subject:(Abacavir)

Universiteit Utrecht

1. Boettiger, D.C. The clinical utility of pharmacogenetic associations in HIV therapy.

Degree: 2011, Universiteit Utrecht

URL: http://dspace.library.uu.nl:8080/handle/1874/203507

► The introduction of HAART has had a remarkably positive impact on HIV patient survival. However individual genetic variability can significantly affect patient response to drugs.… (more)

Subjects/Keywords: HIV; HAART; antiretroviral; pharmacogenetics; pharmacogenetic testing; abacavir

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Boettiger, D. C. (2011). The clinical utility of pharmacogenetic associations in HIV therapy. (Masters Thesis). Universiteit Utrecht. Retrieved from http://dspace.library.uu.nl:8080/handle/1874/203507

Chicago Manual of Style (16^th Edition):

Boettiger, D C. “The clinical utility of pharmacogenetic associations in HIV therapy.” 2011. Masters Thesis, Universiteit Utrecht. Accessed March 07, 2021. http://dspace.library.uu.nl:8080/handle/1874/203507.

MLA Handbook (7^th Edition):

Boettiger, D C. “The clinical utility of pharmacogenetic associations in HIV therapy.” 2011. Web. 07 Mar 2021.

Vancouver:

Boettiger DC. The clinical utility of pharmacogenetic associations in HIV therapy. [Internet] [Masters thesis]. Universiteit Utrecht; 2011. [cited 2021 Mar 07]. Available from: http://dspace.library.uu.nl:8080/handle/1874/203507.

Council of Science Editors:

Boettiger DC. The clinical utility of pharmacogenetic associations in HIV therapy. [Masters Thesis]. Universiteit Utrecht; 2011. Available from: http://dspace.library.uu.nl:8080/handle/1874/203507

Kristianstad University

2. Håkansson, Cornelia. Jämförelse mellan två analyskit för typning av det humana leukocytantigenet HLA-B*57.

Degree: Education and Environment, 2017, Kristianstad University

URL: http://urn.kb.se/resolve?urn=urn:nbn:se:hkr:diva-16931

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Humana leukocytantigen (HLA) är en typ av proteiner som uttrycks på alla cellers yta, de karakteriseras som antigenpresenterande och är en mekanism som ryggradsdjur… (more)

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Humana leukocytantigen (HLA) är en typ av proteiner som uttrycks på alla cellers yta, de karakteriseras som antigenpresenterande och är en mekanism som ryggradsdjur utvecklat för att lokalisera infekterade eller defekta celler. HLA presenterar peptider från cellens insida för immunförsvaret, vilket i sin tur aktiverar andra delar av immunförsvaret eller inducerar apoptos om främmande peptider presenteras. HIV är ett virus som infekterar celler som uttrycker CD4 på ytan, så som makrofager och T-hjälparceller som ingår i immunförsvaret. Dessa sjunker i antal och immunförsvaret blir försvagat. Obehandlad HIV leder till AIDS, därför är bromsmediciner som Abacavir viktigt. Abacavir har visat goda resultat, dock drabbas 5-8% av hypersensitivitetsreaktioner. Forskare har visat att dessa reaktioner är starkt relaterade till HLA-B*57:01 allelen. Genom screening av denna allel kan behandling med Abacavir undvikas för denna grupp patienter. Syftet med denna studie var att jämföra två olika kit, Olerup SSP® HLA-B*57:01 och Inno-train HLA-READY GENE B57, för typning av HLA-B*57 i 20 olika DNA prover. Dessa jämfördes med den befintliga metoden för HLA-typning som används på klinisk immunologi och transfusionsmedicin, Universitetssjukhuset, Lund. Jämförelsen grundade sig på skillnader mellan kiten, både vad gäller resultat, kostnader och analystider. Proverna analyserades med PCR innan de separerades på agarosgel med gelelektrofores. Resultaten tolkades enligt tillverkarnas anvisningar. Resultaten visade att båda metoderna kan typa HLA korrekt. Alla resultat med Olerup stämde. Däremot blev 8 av 20 prover fel vid första körningen med Inno-train men resultaten stämde efter omkörning. Avseende kostnader är Inno-train billigare per prov men Olerup skulle bli billigare långsiktigt. För att verkligen fastställa vilket kit som är mest lämpligt behövs fler analyser utföras.

Human leokocyte antigen (HLA), a protein present on the surface of our cells, is characterized as antigen-presenting a mechanism vertebrates have developed to locate infected or defect cells. HLA presents peptides which are brought from the cell's inside to be presented for the immune system. HIV is a virus that infects cells that express CD4 on the surface, such as macrophages and T-helper cells. When these are decreasing, the immune system gets weakened. Untreated HIV leads to AIDS, therefore are inhibiting pharmaceuticals like Abacavir important. Abacavir has shown good results, unfortunately 5-8% gets hypersensitivity-reactions. Scientists have shown that these reactions are strongly related to the HLA-B*57:01 allele. By screening for this allele, treatment with Abacavir could be avoided for this group of patients. The purpose of this study was to compare two different kits, Olerup SSP® HLA-B*57:01 and Inno-train HLA-READY GENE B57, for screening of HLA-B*57 in 20 different DNA samples. These have previously been typed with the established method at the clinical immunology and transfusion medicine, Lund University Hospital. The…

Subjects/Keywords: HIV; HLA; Abacavir; Hypersensitivity; PCR; HIV; HLA; Abacavir; Hypersensitivitet; PCR; Immunology; Immunologi

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Håkansson, C. (2017). Jämförelse mellan två analyskit för typning av det humana leukocytantigenet HLA-B*57. (Thesis). Kristianstad University. Retrieved from http://urn.kb.se/resolve?urn=urn:nbn:se:hkr:diva-16931

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Håkansson, Cornelia. “Jämförelse mellan två analyskit för typning av det humana leukocytantigenet HLA-B*57.” 2017. Thesis, Kristianstad University. Accessed March 07, 2021. http://urn.kb.se/resolve?urn=urn:nbn:se:hkr:diva-16931.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Håkansson, Cornelia. “Jämförelse mellan två analyskit för typning av det humana leukocytantigenet HLA-B*57.” 2017. Web. 07 Mar 2021.

Vancouver:

Håkansson C. Jämförelse mellan två analyskit för typning av det humana leukocytantigenet HLA-B*57. [Internet] [Thesis]. Kristianstad University; 2017. [cited 2021 Mar 07]. Available from: http://urn.kb.se/resolve?urn=urn:nbn:se:hkr:diva-16931.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Håkansson C. Jämförelse mellan två analyskit för typning av det humana leukocytantigenet HLA-B*57. [Thesis]. Kristianstad University; 2017. Available from: http://urn.kb.se/resolve?urn=urn:nbn:se:hkr:diva-16931

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

3. Claudineia de Araújo Nogueira. Screening do alelo HLA-B*5701 em associação a hipersensibilidade ao abacavir em pacientes HIV positivos do estado de Mato Grosso.

Degree: 2010, Universidade Federal de São Paulo

URL: http://www.bdtd.unifesp.br/tede//tde_busca/arquivo.php?codArquivo=2494 ; http://www.bdtd.unifesp.br/tede//tde_busca/arquivo.php?codArquivo=2495

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Hypersensitivity reaction to abacavir is strongly associated with the presence of the HLA-B*57:01 allele. This study was designed to establish the prevalence of HLA-B*57:01 among… (more)

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Hypersensitivity reaction to abacavir is strongly associated with the presence of the HLA-B*57:01 allele. This study was designed to establish the prevalence of HLA-B*57:01 among HIV-1 infected individuals in Brazil. A total of 517 consecutive outpatients clinics of the State Reference Center in High and Medium Complexity - CERMAC and forwarded to other medical care unit of the Mato Grosso State were followed in this study from february 2008 through july 2010. The presence of HLA-B*57:01 was determined by Nested-PCR with HLA-B*57 and HLA-B*57:01 sequence-specific primers (PCR-SSP). A total of 517 patients were enrolled and randomly assigned to a study group. Of these, 385 (74.5%) were negative for HLA-B*57; 103 (19.9%) were positive for HLA-B*57 and 29 (5.6%) were positive for HLA-B*57:01. Of the HLA-B*57 and HLA-B*57:01 negative patients, the median age was 40 years; 205 (53.2%) were male sex and 242 (62.9%) were Caucasians. Among the patients positive for allele HLA-B*57, the mean age were 38 years; 47 (45.6%) were male sex and 64 (62.1%) were Caucasians. Of the patients positive for allele HLA-B*57:01, the median age was 40 years; 17 (58.6%) were men and 15 (57.7%) were caucasian. An abacavir containing regimen was administerede to 68 patients during the study period, the HLA-B*57:01 alelle was found in 7 (10.3%) of these and the in Hypersensitivity reaction was clinically diagnosed in 4 of these patients, with a statistically significant incidence (p<0.001).

Introdução: Desde a introdução da terapia antirretroviral altamente ativa, infecções como as que ocorrem pelo vírus da Imunodeficiência Humana (HIV) passaram a ser tratadas como uma condição crônica manejável e não mais como uma doença fatal. A suspeita de hipersensibilidade é a principal razão para o início da interrupção do abacavir. O desenvolvimento desta hipersensibilidade por pacientes infectados com o vírus HIV ainda não está completamente esclarecido. Testes genéticos que comprovam a presença do alelo HLA-B*57:01 e permitem a exclusão do uso do abacavir por pacientes portadores deste alelo o que têm demonstrado uma diminuição da incidência de hipersensibilidade entre indivíduos portadores deste vírus. Objetivo: Verificar a prevalência do alelo HLA-B*57 e do alelo específico HLA-B* 57:01 nos pacientes HIV positivos em tratamento com antirretrovirais no Estado de Mato Grosso e estabelecer a eficácia do rastreio prospectivo do alelo específico para impedir a reação de hipersensibilidade ao abacavir. Métodos: As genotipagens para a detecção do alelo HLA-B*5701 foram realizadas por PCR-SSP (Polymerase Chain Reaction - Sequence Specific of Primers) utlilizando um multiplex contendo quatro seqüências dos pares de oligonucleotídios iniciadores. Participaram do estudo 517 pacientes portadores do vírus HIV em tratamento no Centro Estadual de Referência em Média e Alta Complexidade CERMAC DST/AIDS e/ou encaminhados de outras Unidades de atendimento médico do Estado de Mato Grosso. Resultados: Dos 517 pacientes incluídos no estudo, 385 (74,5%) tiveram…

Advisors/Committee Members: Luis Garcia Alonso, Ismael Dale Cotrim Guerreiro da Silva, Regina Affonso, Patricia Pasquali Parise Maltempi, Renata Dezengrini Slhessarenko.

Subjects/Keywords: HIV; PCR; HLA-B*57:01; Alelo HLA-B*57:01; Abacavir; Hipersensibilidade; GINECOLOGIA E OBSTETRICIA; HIV patients; Abacavir

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Nogueira, C. d. A. (2010). Screening do alelo HLA-B*5701 em associação a hipersensibilidade ao abacavir em pacientes HIV positivos do estado de Mato Grosso. (Thesis). Universidade Federal de São Paulo. Retrieved from http://www.bdtd.unifesp.br/tede//tde_busca/arquivo.php?codArquivo=2494 ; http://www.bdtd.unifesp.br/tede//tde_busca/arquivo.php?codArquivo=2495

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Nogueira, Claudineia de Araújo. “Screening do alelo HLA-B*5701 em associação a hipersensibilidade ao abacavir em pacientes HIV positivos do estado de Mato Grosso.” 2010. Thesis, Universidade Federal de São Paulo. Accessed March 07, 2021. http://www.bdtd.unifesp.br/tede//tde_busca/arquivo.php?codArquivo=2494 ; http://www.bdtd.unifesp.br/tede//tde_busca/arquivo.php?codArquivo=2495.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Nogueira, Claudineia de Araújo. “Screening do alelo HLA-B*5701 em associação a hipersensibilidade ao abacavir em pacientes HIV positivos do estado de Mato Grosso.” 2010. Web. 07 Mar 2021.

Vancouver:

Nogueira CdA. Screening do alelo HLA-B*5701 em associação a hipersensibilidade ao abacavir em pacientes HIV positivos do estado de Mato Grosso. [Internet] [Thesis]. Universidade Federal de São Paulo; 2010. [cited 2021 Mar 07]. Available from: http://www.bdtd.unifesp.br/tede//tde_busca/arquivo.php?codArquivo=2494 ; http://www.bdtd.unifesp.br/tede//tde_busca/arquivo.php?codArquivo=2495.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Nogueira CdA. Screening do alelo HLA-B*5701 em associação a hipersensibilidade ao abacavir em pacientes HIV positivos do estado de Mato Grosso. [Thesis]. Universidade Federal de São Paulo; 2010. Available from: http://www.bdtd.unifesp.br/tede//tde_busca/arquivo.php?codArquivo=2494 ; http://www.bdtd.unifesp.br/tede//tde_busca/arquivo.php?codArquivo=2495

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Universidade Nova

4. Grilo, Nádia Filipa Marques. Protein adducts from the anti-HIV drug abacavir – possible biomarkers of drug toxicity.

Degree: 2012, Universidade Nova

URL: http://www.rcaap.pt/detail.jsp?id=oai:run.unl.pt:10362/8203

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Dissertação para obtenção do Grau de Mestre em Genética Molecular e Biomedicina

While the benefits of combined antiretroviral therapy have revolutionized the life expectancy of… (more)

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Dissertação para obtenção do Grau de Mestre em Genética Molecular e Biomedicina

While the benefits of combined antiretroviral therapy have revolutionized the life expectancy of patients infected with the human immunodeficiency virus, treatment-associated toxicity is frequently observed. Abacavir is a nucleoside reverse transcriptase inhibitor associated with acute toxic events,such as hypersensitivity reactions. In addition, its long-term use has increasingly been recognized as associated with an increased risk of myocardial infarction. While the mechanisms underlying abacavirinduced hypersensitivity and cardiotoxicity are not fully understood, abacavir bioactivation to a reactive aldehyde metabolite is thought to play a crucial role in this context. However, as a short lived specie,in vivo, its formation has so far eluded detection. Our initial hypothesis was that it could be efficiently trapped by N-terminal valine of hemoglobin, forming N-terminal-valine-abacavir adducts. With the ultimate goal of gain insight into the role of abacavir metabolism in abacavir-induced toxicity, the present work was focused on obtaining evidence for the abacavir bioactivation to a reactive aldehyde metabolite, in human immunodeficiency virus - infected patients, and on the evaluation of this reactive metabolite ability to undergo protein modification. To address these issues: 1) abacavir-Edman standards were prepared to monitor the presence of these adducts in vivo; 2) the presence of abacavir-Edman adduct was screened in Wistar rats, for optimization of analytical method; and 3) in patients infected with the human immunodeficiency virus. The experimental approach used, involving N-Alkyl Edman degradation, for specific detachment of N-terminal-valineabacavir adducts from protein, followed by liquid chromatography-electrospray ionization tandem mass spectrometry analysis of detached abacavir-Edman adducts, upon comparison with standards prepared in vitro, allowed the unequivocal identification of these adducts in animal and human samples. These results represent the first report on the involvement of a conjugated aldehyde intermediate in the metabolic activation of abacavir in man. Whereas this evidence does not imply an exclusive relation between abacavir-Edman adducts and abacavir toxicity, the search for causal relationships between the formation of abacabir-derived protein adducts and the occurrence of abacavir-induced toxic events in patients is worth pursuing, and is currently underway, towards the clarification of mechanism(s) of abacavir-induced toxicity.

Advisors/Committee Members: Pereira, Sofia, Antunes, Alexandra.

Subjects/Keywords: Abacavir; Aldehyde metabolite; Biomarker; Cardiotoxicity; Drug bioactivation; Hypersensitivity

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Grilo, N. F. M. (2012). Protein adducts from the anti-HIV drug abacavir – possible biomarkers of drug toxicity. (Thesis). Universidade Nova. Retrieved from http://www.rcaap.pt/detail.jsp?id=oai:run.unl.pt:10362/8203

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Grilo, Nádia Filipa Marques. “Protein adducts from the anti-HIV drug abacavir – possible biomarkers of drug toxicity.” 2012. Thesis, Universidade Nova. Accessed March 07, 2021. http://www.rcaap.pt/detail.jsp?id=oai:run.unl.pt:10362/8203.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Grilo, Nádia Filipa Marques. “Protein adducts from the anti-HIV drug abacavir – possible biomarkers of drug toxicity.” 2012. Web. 07 Mar 2021.

Vancouver:

Grilo NFM. Protein adducts from the anti-HIV drug abacavir – possible biomarkers of drug toxicity. [Internet] [Thesis]. Universidade Nova; 2012. [cited 2021 Mar 07]. Available from: http://www.rcaap.pt/detail.jsp?id=oai:run.unl.pt:10362/8203.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Grilo NFM. Protein adducts from the anti-HIV drug abacavir – possible biomarkers of drug toxicity. [Thesis]. Universidade Nova; 2012. Available from: http://www.rcaap.pt/detail.jsp?id=oai:run.unl.pt:10362/8203

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Melbourne

5. Illing, Patricia Therese. An abacavir induced change in self-presentation by HLA-B*57:01 causes Abacavir Hypersensitivity Syndrome.

Degree: 2013, University of Melbourne

URL: http://hdl.handle.net/11343/38547

► In recent years, numerous associations between adverse drug reactions (ADRs) and specific alleles of the Human Leukocyte Antigen (HLA) genes have been discovered, however the… (more)

▼ In recent years, numerous associations between adverse drug reactions (ADRs) and specific alleles of the Human Leukocyte Antigen (HLA) genes have been discovered, however the mechanisms behind these associations are poorly understood. The HLA molecules are highly polymorphic cell surface glycoproteins involved in the presentation of both self and pathogen derived peptides at the cell surface for immune surveillance. Under normal circumstances, presented peptides derived from self-proteins are ignored, however novel peptides, such as those derived from invading pathogens, are recognised by circulating T cells stimulating a peptide-specific immune response. This has led to the hypothesis that HLA associated ADRs are due to a specific interaction between the drug and the associated HLA allotype that stimulates inappropriate immune activation. At the outset of this study no such interaction had been shown. Abacavir hypersensitivity syndrome (AHS) is a T cell mediated drug hypersensitivity that occurs exclusively in individuals possessing the HLA class I allele HLA-B*57:01. With an odds ratio greater than 900, this is one of the strongest HLA/disease associations identified to date. It was therefore the aim of this study to clarify the role of HLA-B*57:01 in abacavir induced T cell activation, in the hope of providing a model for allotype specific involvement of HLA molecules in ADRs. Using a combination of mass spectrometry and x-ray crystallography, this study showed that abacavir bound within the peptide binding cleft of HLA-B*57:01, lying across a cluster of amino acid residues that are polymorphic between HLA-B*57:01 and closely related, non-AHS associated, allotypes. Furthermore, partial occlusion of the F-pocket, a region of the antigen-binding cleft that accommodates the C-terminal residue of the bound peptide, resulted in a change in the nature of the peptides that could be accommodated within the cleft in the presence of abacavir. Whilst in the absence of abacavir HLA-B*57:01 bound peptides possessing the bulky aromatic residues tryptophan and phenylalanine at the C-terminus, in the presence of abacavir it showed an increased preference for peptides terminating in smaller aliphatic residues, primarily isoleucine and leucine. This resulted in an approximate 25-30 % change in the abundant peptides presented at the cell surface by HLA-B*57:01, furnishing a large number of potentially immunogenic, novel HLA-B*57:01-abacavir-peptide complexes for immune surveillance. Consistent with a large number of immunogenic HLA complexes, the T cell response against abacavir treated HLA-B*57:01+ cells was shown to be highly diverse, and responses to a specific HLA-B*57:01-abacavir-peptide complex were isolated. Overall these data strongly suggest that by occupying the peptide-binding cleft of HLA-B*57:01, abacavir creates an altered display of immunological self which stimulates T cell mediated self-reactivity and manifests…

Subjects/Keywords: immunology; Human Leukocyte Antigen; hypersensitivity; abacavir; adverse drug reaction

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Illing, P. T. (2013). An abacavir induced change in self-presentation by HLA-B*57:01 causes Abacavir Hypersensitivity Syndrome. (Doctoral Dissertation). University of Melbourne. Retrieved from http://hdl.handle.net/11343/38547

Chicago Manual of Style (16^th Edition):

Illing, Patricia Therese. “An abacavir induced change in self-presentation by HLA-B*57:01 causes Abacavir Hypersensitivity Syndrome.” 2013. Doctoral Dissertation, University of Melbourne. Accessed March 07, 2021. http://hdl.handle.net/11343/38547.

MLA Handbook (7^th Edition):

Illing, Patricia Therese. “An abacavir induced change in self-presentation by HLA-B*57:01 causes Abacavir Hypersensitivity Syndrome.” 2013. Web. 07 Mar 2021.

Vancouver:

Illing PT. An abacavir induced change in self-presentation by HLA-B*57:01 causes Abacavir Hypersensitivity Syndrome. [Internet] [Doctoral dissertation]. University of Melbourne; 2013. [cited 2021 Mar 07]. Available from: http://hdl.handle.net/11343/38547.

Council of Science Editors:

Illing PT. An abacavir induced change in self-presentation by HLA-B*57:01 causes Abacavir Hypersensitivity Syndrome. [Doctoral Dissertation]. University of Melbourne; 2013. Available from: http://hdl.handle.net/11343/38547

6. Fauchet, Floris. Optimisation pharmacocinétique du traitement de la femme enceinte et de l'enfant infectés par le VIH, par une approche de population : Pharmacokinetic optimization treatment of HIV-infected pregnant women and children, use of a population approach.

Degree: Docteur es, Pharmacologie, 2014, Université Paris Descartes – Paris V

URL: http://www.theses.fr/2014PA05P632

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L’utilisation d’un traitement antirétroviral, chez la femme enceinte ou chez l’enfant infecté par le VIH, doit être optimale en termes d’efficacité et de tolérance. De… (more)

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L’utilisation d’un traitement antirétroviral, chez la femme enceinte ou chez l’enfant infecté par le VIH, doit être optimale en termes d’efficacité et de tolérance. De nombreuses modifications physiologiques ont lieu tout au long de la grossesse ainsi que pendant les premières années de vie d’un enfant. Ces changements peuvent intervenir à tous les niveaux du devenir du médicament dans l’organisme. Une mauvaise connaissance des variations pharmacocinétiques associées à ces changements physiologiques peut amener à une toxicité ou à une inefficacité de ces traitements. Il est donc primordial de connaître la pharmacocinétique des différentes molécules antirétrovirales recommandées chez la femme enceinte et l’enfant infectés par le VIH. Les pharmacocinétiques de deux inhibiteurs non nucléosidiques de la transcriptase inverse, la zidovudine et l’abacavir et celle d'un inhibiteur de protéase, le lopinavir, ont été étudiées chez la femme enceinte et/ou chez l'enfant par une approche de population. L’évaluation et l’optimisation des recommandations posologiques de ces trois molécules ont été réalisées en tenant compte de relations concentration-effet et/ou concentration-toxicité précédemment établies. L'étude décrivant la pharmacocinétique de l’abacavir a montré qu’une adaptation posologique n’était pas nécessaire pendant la grossesse. En revanche, les études sur la pharmacocinétique de la zidovudine ont montré que les doses recommandées, chez la femme enceinte et chez l’enfant, devraient être diminuées afin de limiter les risques de toxicité. Pour finir, l’étude sur la pharmacocinétique du lopinavir a suggéré qu’il n’était pas nécessaire d’augmenter les posologies pendant la grossesse, contrairement à ce qui est recommandé dans la littérature.

The use of an antiretroviral therapy in pregnant women or in HIV-infected child should be optimal in terms of efficacy and safety. Important physiological changes occur during pregnancy and the first years of life. These changes can affect drug pharmacokinetics. Poor knowledge of pharmacokinetic variations associated with these physiological changes can lead to toxicity or failure of these treatments. Therefore, it is important to know the antiretroviral pharmacokinetics of recommended drugs in pregnant women and in HIV-infected children. The pharmacokinetics of two nucleoside reverse transcriptase inhibitors, zidovudine and abacavir and one protease inhibitor, lopinavir, have been studied in pregnant women and/or in children with a population approach. The evaluation and optimization of dosage recommendations of these three molecules have been achieved using concentration-efficacy and/or concentration-toxicity relationships previously established. The study describing the abacavir pharmacokinetics showed that a dose adjustment was not necessary during pregnancy. However, studies on zidovudine pharmacokinetics presented that the doses recommended in pregnant women and in children should be reduced in order to limit the toxicity risks. Finally, the study on lopinavir…

Advisors/Committee Members: Tréluyer, Jean-Marc (thesis director).

Subjects/Keywords: VIH; Femme enceinte; Prévention mère-enfant; Pharmacocinétique de population; Passage transplacentaire; Zidovudine; Lopinavir; Abacavir; HIV; Pregnant women; PMTCT; Population pharmacokinetics; Placental transfer; Zidovudine; Lopinavir; Abacavir; 615.7

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Fauchet, F. (2014). Optimisation pharmacocinétique du traitement de la femme enceinte et de l'enfant infectés par le VIH, par une approche de population : Pharmacokinetic optimization treatment of HIV-infected pregnant women and children, use of a population approach. (Doctoral Dissertation). Université Paris Descartes – Paris V. Retrieved from http://www.theses.fr/2014PA05P632

Chicago Manual of Style (16^th Edition):

Fauchet, Floris. “Optimisation pharmacocinétique du traitement de la femme enceinte et de l'enfant infectés par le VIH, par une approche de population : Pharmacokinetic optimization treatment of HIV-infected pregnant women and children, use of a population approach.” 2014. Doctoral Dissertation, Université Paris Descartes – Paris V. Accessed March 07, 2021. http://www.theses.fr/2014PA05P632.

MLA Handbook (7^th Edition):

Fauchet, Floris. “Optimisation pharmacocinétique du traitement de la femme enceinte et de l'enfant infectés par le VIH, par une approche de population : Pharmacokinetic optimization treatment of HIV-infected pregnant women and children, use of a population approach.” 2014. Web. 07 Mar 2021.

Vancouver:

Fauchet F. Optimisation pharmacocinétique du traitement de la femme enceinte et de l'enfant infectés par le VIH, par une approche de population : Pharmacokinetic optimization treatment of HIV-infected pregnant women and children, use of a population approach. [Internet] [Doctoral dissertation]. Université Paris Descartes – Paris V; 2014. [cited 2021 Mar 07]. Available from: http://www.theses.fr/2014PA05P632.

Council of Science Editors:

Fauchet F. Optimisation pharmacocinétique du traitement de la femme enceinte et de l'enfant infectés par le VIH, par une approche de population : Pharmacokinetic optimization treatment of HIV-infected pregnant women and children, use of a population approach. [Doctoral Dissertation]. Université Paris Descartes – Paris V; 2014. Available from: http://www.theses.fr/2014PA05P632

University of California – Berkeley

7. Dorjee, Kunchok. Cardiovascular Disease Outcomes from Use of Antiretroviral Agents Among HIV-infected Individuals.

Degree: Epidemiology, 2016, University of California – Berkeley

URL: http://www.escholarship.org/uc/item/0fc9w43d

► Cardiovascular Disease Outcomes from Use of Antiretroviral Agents Among HIV-infected Individuals ByKunchok DorjeeDoctor of Philosophy in EpidemiologyUniversity of California, BerkeleyProfessor Arthur L. Reingold, ChairCombination anti-retroviral… (more)

▼ Cardiovascular Disease Outcomes from Use of Antiretroviral Agents Among HIV-infected Individuals ByKunchok DorjeeDoctor of Philosophy in EpidemiologyUniversity of California, BerkeleyProfessor Arthur L. Reingold, ChairCombination anti-retroviral therapy (ART) has improved the quality of life of Human Immunodeficiency Virus (HIV)-infected individuals, and has helped them to live longer. A better understanding of the adverse drug events associated with use of various antiretroviral (ARV) drugs can help in further improving the health outcomes of HIV-infected patients. In the past years, use of various individual and combinations of ARV agents have been shown to be associated with an increased risk of cardiovascular disease (CVD) among HIV-infected patients. Of the various ARV agents, the propensity of abacavir, a nucleoside reverse transcriptase inhibitor, to increase the risk of CVD has received particular attention because of its central role as an anchor drug in combination ART. This dissertation aims to investigate the risk of acute myocardial infarction (AMI) associated with use of various antiretroviral agents among HIV-infected individuals in the United States. It further presents the results of an in-depth analysis of the risk of CVD associated with use of abacavir among HIV-infected individuals. Additionally, the results of a systematic review and meta-analysis of epidemiologic studies that were carried out to assess the risk of CVD associated with abacavir use are also presented in this dissertation. Because a number of covariates that could potentially confound the relationship between use of ARV agents and the risk of CVD may also lie on the causal pathway, and because these factors could potentially be influenced by receipt of the exposure in the past, marginal structural Cox proportional hazard models using stabilized inverse probability of treatment weights were used to investigate this relationship. Results from unweighted Cox regressions were additionally presented for comparison. For the systematic review and meta-analysis, random-effects models were used when there was heterogeneity of results across studies, and fixed-effects models were used when there was no heterogeneity. The fixed-effects and random-effects models were weighted by inverse of variance. Chapter One of this dissertation describes the risk of AMI associated with use of several individual and combinations of ARV agents among HIV-infected patients receiving ART. The risk of AMI was elevated among HIV-infected individuals currently exposed to abacavir, lamivudine, didanosine, lopinavir, and darunavir. Of the ARV drug combinations, current exposure to combinations of abacavir+lamivudine+atazanavir, abacavir+lamivudine+darunavir, and tenofovir+emtricitabine+raltegravir was associated with an increased risk of developing AMI. There was a protective effect against AMI from exposures to tenofovir, emtricitabine, and efavirenz, as individual agents, and as a combination regimen. Chapter Two of this dissertation presents the results of a…

Subjects/Keywords: Medicine; Epidemiology; Public health; Abacavir; Antiretroviral Therapy; Cardiovascular disease; HIV infection; Myocardial Infarction

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Dorjee, K. (2016). Cardiovascular Disease Outcomes from Use of Antiretroviral Agents Among HIV-infected Individuals. (Thesis). University of California – Berkeley. Retrieved from http://www.escholarship.org/uc/item/0fc9w43d

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Dorjee, Kunchok. “Cardiovascular Disease Outcomes from Use of Antiretroviral Agents Among HIV-infected Individuals.” 2016. Thesis, University of California – Berkeley. Accessed March 07, 2021. http://www.escholarship.org/uc/item/0fc9w43d.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Dorjee, Kunchok. “Cardiovascular Disease Outcomes from Use of Antiretroviral Agents Among HIV-infected Individuals.” 2016. Web. 07 Mar 2021.

Vancouver:

Dorjee K. Cardiovascular Disease Outcomes from Use of Antiretroviral Agents Among HIV-infected Individuals. [Internet] [Thesis]. University of California – Berkeley; 2016. [cited 2021 Mar 07]. Available from: http://www.escholarship.org/uc/item/0fc9w43d.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Dorjee K. Cardiovascular Disease Outcomes from Use of Antiretroviral Agents Among HIV-infected Individuals. [Thesis]. University of California – Berkeley; 2016. Available from: http://www.escholarship.org/uc/item/0fc9w43d

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of KwaZulu-Natal

8. Montgomery, Stephane. Comparison of virological responses of children commenced on an abacavir versus stavudine based antiretroviral regimen at King Edward VIII Hospital : Durban.

Degree: 2016, University of KwaZulu-Natal

URL: http://hdl.handle.net/10413/15369

► Background: UNAIDS estimated that in 2014 just over 160 000 children in South Africa were receiving HAART, accounting for 20% of the global HAART cohort.… (more)

▼ Background: UNAIDS estimated that in 2014 just over 160 000 children in South Africa were receiving HAART, accounting for 20% of the global HAART cohort. Finding the appropriate HAART regimen that is safe, well tolerated and efficacious is of extreme importance in ensuring continued and ongoing success of the Paediatric HAART program. In 2010 the World Health Organisation, due to concerns of short and long term stavudine toxicity changed the recommendation regarding first-line HAART regimen from a stavudine based regimen. In South Africa, an abacavir based regimen was chosen as the preferred background regimen. However questions have been raised as to whether this change has replaced the safety concerns associated with stavudine with a less efficacious regimen. Method: A Retrospective chart review was conducted to evaluate the virological responses at 6 and 12 months in a cohort of children initiated on an abacavir based regimen at King Edward VIII hospital between January 2012 – December 2012. Data of 94 children under the age of 12 years who were initiated on abacavir and lamivudine with either lopinavir/ritonavir or efavirenz regimen (abacavir cohort) were analysed using Fisher’s exact test and logistical regression to evaluate virological suppression at 12 months. The data was compared to a prior retrospective chart review conducted between 2004 – 2010 at King Edward VIII Hospital during which a stavudine and lamivudine with either Lopinavir/ritonavir or efavirenz (stavudine cohort) was the standard of care. Results: In both the abacavir cohort and stavudine cohort there was no difference in gender distribution and the mean age of initiation was 6years. In the abacavir cohort, 62,8% were initiated on ABC/3TC/EFV and 37,2% on ABC/3TC/KAL. 88,4% were initiated on D4T/3TC/EFV and 11,6% were initiated on D4T/3TC/KAL in the stavudine cohort. The virological suppression rate in the abacavir cohort was 80.7% compared to 85.2% in the stavudine cohort, which was not a significant difference (p= 0,38:). In the abacavir cohort there was no statistical significant difference in virological suppression between patients on efavirenz versus lopinavir/ritonavir (p= 0.427:). Conclusion: This study demonstrates that children treated with an abacavir based regimen have a good probability of virological suppression, and there was no statistical difference between patients initiating an abacavir-based regimen versus a stavudine based regimen. These findings are in keeping with data from several clinical trials and support the WHO recommendation of an abacavir-based regimen for infants and children initiating antiretroviral treatment. Advisors/Committee Members: Archary, M. (advisor).

Subjects/Keywords: HAART- highly active antiretroviral therapy.; Abacavir.; HIV/AIDS.; PMTCT- prevention of mother to child transmission.

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Montgomery, S. (2016). Comparison of virological responses of children commenced on an abacavir versus stavudine based antiretroviral regimen at King Edward VIII Hospital : Durban. (Thesis). University of KwaZulu-Natal. Retrieved from http://hdl.handle.net/10413/15369

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Montgomery, Stephane. “Comparison of virological responses of children commenced on an abacavir versus stavudine based antiretroviral regimen at King Edward VIII Hospital : Durban.” 2016. Thesis, University of KwaZulu-Natal. Accessed March 07, 2021. http://hdl.handle.net/10413/15369.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Montgomery, Stephane. “Comparison of virological responses of children commenced on an abacavir versus stavudine based antiretroviral regimen at King Edward VIII Hospital : Durban.” 2016. Web. 07 Mar 2021.

Vancouver:

Montgomery S. Comparison of virological responses of children commenced on an abacavir versus stavudine based antiretroviral regimen at King Edward VIII Hospital : Durban. [Internet] [Thesis]. University of KwaZulu-Natal; 2016. [cited 2021 Mar 07]. Available from: http://hdl.handle.net/10413/15369.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Montgomery S. Comparison of virological responses of children commenced on an abacavir versus stavudine based antiretroviral regimen at King Edward VIII Hospital : Durban. [Thesis]. University of KwaZulu-Natal; 2016. Available from: http://hdl.handle.net/10413/15369

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Georgia

9. Lewis, Summer Renee. Maternal and fetal disposition of antiviral agents in the pregnant rat.

Degree: 2014, University of Georgia

URL: http://hdl.handle.net/10724/23173

► Human immunodeficiency virus type-1 (HIV) infection has increased dramatically in pregnant women, thus, exposing the fetus in utero. However, with the increasing use of combination… (more)

Subjects/Keywords: Pharmacokinetics; HIV; Abacavir; Lamivudine; 3TC; Zidovudine; AZT; placental transport; antiviral; fetal disposition

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Lewis, S. R. (2014). Maternal and fetal disposition of antiviral agents in the pregnant rat. (Thesis). University of Georgia. Retrieved from http://hdl.handle.net/10724/23173

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Lewis, Summer Renee. “Maternal and fetal disposition of antiviral agents in the pregnant rat.” 2014. Thesis, University of Georgia. Accessed March 07, 2021. http://hdl.handle.net/10724/23173.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Lewis, Summer Renee. “Maternal and fetal disposition of antiviral agents in the pregnant rat.” 2014. Web. 07 Mar 2021.

Vancouver:

Lewis SR. Maternal and fetal disposition of antiviral agents in the pregnant rat. [Internet] [Thesis]. University of Georgia; 2014. [cited 2021 Mar 07]. Available from: http://hdl.handle.net/10724/23173.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Lewis SR. Maternal and fetal disposition of antiviral agents in the pregnant rat. [Thesis]. University of Georgia; 2014. Available from: http://hdl.handle.net/10724/23173

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

10. Tada, Kohei. Abacavir, an anti-HIV-1 drug, targets TDP1-deficient adult T cell leukemia : 抗HIV薬アバカビルは、TDP1が欠損している成人T細胞白血病を標的とする.

Degree: 博士(医学), 2015, Kyoto University / 京都大学

URL: http://hdl.handle.net/2433/202797 ; http://dx.doi.org/10.14989/doctor.k19363

新制・課程博士

甲第19363号

医博第4040号

Subjects/Keywords: Adult T cell leukemia; Abacavir; TDP1; NRTI; chemotherapy

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APA (6^th Edition):

Tada, K. (2015). Abacavir, an anti-HIV-1 drug, targets TDP1-deficient adult T cell leukemia : 抗HIV薬アバカビルは、TDP1が欠損している成人T細胞白血病を標的とする. (Thesis). Kyoto University / 京都大学. Retrieved from http://hdl.handle.net/2433/202797 ; http://dx.doi.org/10.14989/doctor.k19363

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Tada, Kohei. “Abacavir, an anti-HIV-1 drug, targets TDP1-deficient adult T cell leukemia : 抗HIV薬アバカビルは、TDP1が欠損している成人T細胞白血病を標的とする.” 2015. Thesis, Kyoto University / 京都大学. Accessed March 07, 2021. http://hdl.handle.net/2433/202797 ; http://dx.doi.org/10.14989/doctor.k19363.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Tada, Kohei. “Abacavir, an anti-HIV-1 drug, targets TDP1-deficient adult T cell leukemia : 抗HIV薬アバカビルは、TDP1が欠損している成人T細胞白血病を標的とする.” 2015. Web. 07 Mar 2021.

Vancouver:

Tada K. Abacavir, an anti-HIV-1 drug, targets TDP1-deficient adult T cell leukemia : 抗HIV薬アバカビルは、TDP1が欠損している成人T細胞白血病を標的とする. [Internet] [Thesis]. Kyoto University / 京都大学; 2015. [cited 2021 Mar 07]. Available from: http://hdl.handle.net/2433/202797 ; http://dx.doi.org/10.14989/doctor.k19363.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Tada K. Abacavir, an anti-HIV-1 drug, targets TDP1-deficient adult T cell leukemia : 抗HIV薬アバカビルは、TDP1が欠損している成人T細胞白血病を標的とする. [Thesis]. Kyoto University / 京都大学; 2015. Available from: http://hdl.handle.net/2433/202797 ; http://dx.doi.org/10.14989/doctor.k19363

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

North-West University

11. Van der Merwe, Helanie. Evaluation and validation of in vitro assays to determine cell viability for HIV/AIDS expermentation with Pheroid TM technology / Helanie van der Merwe.

Degree: 2008, North-West University

URL: http://hdl.handle.net/10394/4171

► The Southern parts of Africa have the highest prevalence of HIV-infected people and South Africa is the country with the highest number of infections in… (more)

▼ The Southern parts of Africa have the highest prevalence of HIV-infected people and South Africa is the country with the highest number of infections in the world. There is still no cure for AIDS, but anti-HIV medicine can prolong and enhance the quality of life of an HIV infected person. Patient adherence with antiretroviral therapy is extremely low due to difficult dosing intervals, problematic dosage forms, instability of the antiretrovirals (ARVs) and the severe side-effects caused by these drugs; this leads to resistance of HIV to these drugs. Pheroid™ technology is a patented delivery system. Pheroid™ vesicles were used during this study. The entrapment of an active within the Pheroid™ would generally provide a safer, more effective formulation than the active alone. This could mean that the amount of drug needed for treatment of HIV can be decreased while producing fewer adverse effects and reducing the price of treatment. The main objectives of this study were to optimise and validate the cell viability and viral replication assays that can be used in an in vitro viral infection model. The MTT assay was used to asses the viability of the cells and to determine the toxicity of the antiretroviral drugs and Pheroid™ on the cells. HIV-1 assays were evaluated and used to determine the viral replication in the cells. Two different continuous cell lines were chosen for this study, an anchorage dependent GHOST cell line and suspended M7-Luc cells. Both these cell lines were best infected with the SWl virus. SWl is a subtype C, CXCR4 utilising virus. Subtype C is responsible for 60 % of the HIV infections worldwide and is the prevalent subtype in SUb-Saharan Africa .. Infection enhancers were not added to the cells to improve viral infection since it was observed that the Pheroid™ in combination with DEAE-dextran or Polybrene caused cytotoxicity probably by disrupting the cell's membrane. Antioxidants were added to the Pheroid ™ formulation since it was observed that the viability of the cells incubated with the Pheroid™ decreased as the Pheroid ™ matured. The added antioxidants had no significant effect on the cells. Abacavir (ABC) was chosen as the test substance for this study since it showed low cytotoxicity in cell cultures and is water soluble and would not present solubility issues in the media. It was entrapped within the Pheroid™ and its in vitro efficacy and toxicity was tested on HIV-infected and uninfected cell cultures. One directlHIV-specific (p24 antigen ELISA assay) and one indirect (Luciferase) assays were used to asses the inhibition of HIV replication caused by ABC. The p24 antigen ELISA (Enzyme-Linked ImmunoSorbent Assay) assay required a lot of washing steps and were rather expensive to use. The Luciferase assay was only used on the M7-Luc cells; this assay was sensitive, inexpensive and easy to use. The MTT (3-(4,5-demethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) viability assay was used to measure the toxicity caused by the Pheroid ™ and/or ABC on the cells. MTT is a widely used…

Subjects/Keywords: Abacavir (ABC); HIV and AIDS; Luciferase assay; MTT; p24 antigen ELISA assay; Pheroid™; viability; MIV en VIGS; Lewensvatbaarheid

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Van der Merwe, H. (2008). Evaluation and validation of in vitro assays to determine cell viability for HIV/AIDS expermentation with Pheroid TM technology / Helanie van der Merwe. (Thesis). North-West University. Retrieved from http://hdl.handle.net/10394/4171

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Van der Merwe, Helanie. “Evaluation and validation of in vitro assays to determine cell viability for HIV/AIDS expermentation with Pheroid TM technology / Helanie van der Merwe. ” 2008. Thesis, North-West University. Accessed March 07, 2021. http://hdl.handle.net/10394/4171.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Van der Merwe, Helanie. “Evaluation and validation of in vitro assays to determine cell viability for HIV/AIDS expermentation with Pheroid TM technology / Helanie van der Merwe. ” 2008. Web. 07 Mar 2021.

Vancouver:

Van der Merwe H. Evaluation and validation of in vitro assays to determine cell viability for HIV/AIDS expermentation with Pheroid TM technology / Helanie van der Merwe. [Internet] [Thesis]. North-West University; 2008. [cited 2021 Mar 07]. Available from: http://hdl.handle.net/10394/4171.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Van der Merwe H. Evaluation and validation of in vitro assays to determine cell viability for HIV/AIDS expermentation with Pheroid TM technology / Helanie van der Merwe. [Thesis]. North-West University; 2008. Available from: http://hdl.handle.net/10394/4171

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

North-West University

12. Joubert, Ruan. Comparison of drug permeability in rat, pig and human in vitro models / Ruan Joubert .

Degree: 2015, North-West University

URL: http://hdl.handle.net/10394/15321

► A crucial step in the drug discovery and development process is the assessment of membrane permeability properties of new chemical entities and researchers are constantly… (more)

▼ A crucial step in the drug discovery and development process is the assessment of membrane permeability properties of new chemical entities and researchers are constantly searching for cost-effective, high through-put models with as high as possible predictive value. In addition, a thorough understanding of the membrane permeability pathways and metabolism mechanisms are required when evaluating drug disposition and pharmacokinetics. Various in vitro methods/techniques are available to measure the rate of permeation of compounds across epithelial cell membranes to estimate oral drug absorption in humans. The aim of this study is to compare three in vitro models (i.e. excised rat intestinal tissue, excised pig intestinal tissue and Caco-2 human cell cultures) in terms of drug permeability characteristics by means of different techniques including the Ussing type Sweetana-Grass diffusion chamber apparatus, everted sac glass apparatus and the Transwell® plate apparatus. The transport of abacavir sulphate was determined in two directions (i.e. apical-to-basolateral or AP - BL and basolateral-to-apical or BL - AP) across excised rat intestinal tissue, excised pig intestinal tissue and Caco-2 cell monolayers. The test solution was applied to the donor side and samples (200 μl) were drawn from the acceptor side at 20 min intervals for a period of 2 h. The concentration of abacavir in the samples was then measured by means of a validated high performance liquid chromatography (HPLC) method. The transepithelial electrical resistance (TEER) was measured before and after each transport experiment to give an indication of the integrity of the cell membranes. The apparent permeability coefficient (Papp) and efflux ratio (ER) values were calculated and used to compare the different methods and techniques in terms of drug permeation characteristics. All three of the in vitro methods, in all of the techniques employed, showed higher transport of abacavir in the BL - AP direction than in the AP - BL direction. This indicates that all three in vitro methods had intact active efflux transporters over the entire study period. The excised rat intestinal method showed similar drug permeability characteristics in both techniques compared to that of the Caco-2 cell monolayers. In contrast, the excised pig intestinal method only showed similar drug permeability characteristics in the Sweetana-Grass diffusion apparatus when compared to the Caco-2 cell monolayers. This phenomenon can possibly be explained by the relatively large surface area of the pig tissue used in the everted sac technique where the role of physiological and other factors take effect. These factors may include the thickness of the membrane and mucus layer as well as variables such as diet, age, gender and size of the pigs obtained from the abattoir that cannot be controlled.

Subjects/Keywords: In vitro model; Sweetana-Grass diffusion chambers; Everted sac technique; Caco-2 cell monolayers; High through-put models; Abacavir

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Joubert, R. (2015). Comparison of drug permeability in rat, pig and human in vitro models / Ruan Joubert . (Thesis). North-West University. Retrieved from http://hdl.handle.net/10394/15321

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Joubert, Ruan. “Comparison of drug permeability in rat, pig and human in vitro models / Ruan Joubert .” 2015. Thesis, North-West University. Accessed March 07, 2021. http://hdl.handle.net/10394/15321.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Joubert, Ruan. “Comparison of drug permeability in rat, pig and human in vitro models / Ruan Joubert .” 2015. Web. 07 Mar 2021.

Vancouver:

Joubert R. Comparison of drug permeability in rat, pig and human in vitro models / Ruan Joubert . [Internet] [Thesis]. North-West University; 2015. [cited 2021 Mar 07]. Available from: http://hdl.handle.net/10394/15321.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Joubert R. Comparison of drug permeability in rat, pig and human in vitro models / Ruan Joubert . [Thesis]. North-West University; 2015. Available from: http://hdl.handle.net/10394/15321

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

13. Tada, Kohei. Abacavir, an anti-HIV-1 drug, targets TDP1-deficient adult T cell leukemia .

Degree: 2015, Kyoto University

URL: http://hdl.handle.net/2433/202797

Subjects/Keywords: Adult T cell leukemia; Abacavir; TDP1; NRTI; chemotherapy

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Tada, K. (2015). Abacavir, an anti-HIV-1 drug, targets TDP1-deficient adult T cell leukemia . (Thesis). Kyoto University. Retrieved from http://hdl.handle.net/2433/202797

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Tada, Kohei. “Abacavir, an anti-HIV-1 drug, targets TDP1-deficient adult T cell leukemia .” 2015. Thesis, Kyoto University. Accessed March 07, 2021. http://hdl.handle.net/2433/202797.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Tada, Kohei. “Abacavir, an anti-HIV-1 drug, targets TDP1-deficient adult T cell leukemia .” 2015. Web. 07 Mar 2021.

Vancouver:

Tada K. Abacavir, an anti-HIV-1 drug, targets TDP1-deficient adult T cell leukemia . [Internet] [Thesis]. Kyoto University; 2015. [cited 2021 Mar 07]. Available from: http://hdl.handle.net/2433/202797.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Tada K. Abacavir, an anti-HIV-1 drug, targets TDP1-deficient adult T cell leukemia . [Thesis]. Kyoto University; 2015. Available from: http://hdl.handle.net/2433/202797

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Georgia

14. Clark, Teresa Nicole. Quantitative analysis and pharmacokinetics of reverse transcriptase inhibitors in the pregnant rat.

Degree: 2014, University of Georgia

URL: http://hdl.handle.net/10724/21009

► For over two decades there has been a ceaseless search for more effective treatments of HIV/AIDS. Today there are a number of different therapies that… (more)

Subjects/Keywords: Azidouridine; AZDU; Zidovudine; AZT; Abacavir; ABC; Didanosine; DDI; High Performance Liquid Chromatography; HPLC-UV; LC/MS/MS; Pharmacokinetics

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Clark, T. N. (2014). Quantitative analysis and pharmacokinetics of reverse transcriptase inhibitors in the pregnant rat. (Thesis). University of Georgia. Retrieved from http://hdl.handle.net/10724/21009

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Clark, Teresa Nicole. “Quantitative analysis and pharmacokinetics of reverse transcriptase inhibitors in the pregnant rat.” 2014. Thesis, University of Georgia. Accessed March 07, 2021. http://hdl.handle.net/10724/21009.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Clark, Teresa Nicole. “Quantitative analysis and pharmacokinetics of reverse transcriptase inhibitors in the pregnant rat.” 2014. Web. 07 Mar 2021.

Vancouver:

Clark TN. Quantitative analysis and pharmacokinetics of reverse transcriptase inhibitors in the pregnant rat. [Internet] [Thesis]. University of Georgia; 2014. [cited 2021 Mar 07]. Available from: http://hdl.handle.net/10724/21009.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Clark TN. Quantitative analysis and pharmacokinetics of reverse transcriptase inhibitors in the pregnant rat. [Thesis]. University of Georgia; 2014. Available from: http://hdl.handle.net/10724/21009

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

15. Hileman, Corrilynn O. The Effect of Abacavir on Inflammation and Endothelial Cell Activation in Adults with HIV Infection.

Degree: MSs, Epidemiology and Biostatistics, 2010, Case Western Reserve University School of Graduate Studies

URL: http://rave.ohiolink.edu/etdc/view?acc_num=case1270179884

► Abacavir has been associated with increased risk of myocardial infarction in HIV-infected adults. This retrospective cohort study was designed to determine the biologic mechanism. Stored… (more)

Subjects/Keywords: Health; Immunology; Virology; HIV; abacavir; endothelial cell activation; inflammation

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APA (6^th Edition):

Hileman, C. O. (2010). The Effect of Abacavir on Inflammation and Endothelial Cell Activation in Adults with HIV Infection. (Masters Thesis). Case Western Reserve University School of Graduate Studies. Retrieved from http://rave.ohiolink.edu/etdc/view?acc_num=case1270179884

Chicago Manual of Style (16^th Edition):

Hileman, Corrilynn O. “The Effect of Abacavir on Inflammation and Endothelial Cell Activation in Adults with HIV Infection.” 2010. Masters Thesis, Case Western Reserve University School of Graduate Studies. Accessed March 07, 2021. http://rave.ohiolink.edu/etdc/view?acc_num=case1270179884.

MLA Handbook (7^th Edition):

Hileman, Corrilynn O. “The Effect of Abacavir on Inflammation and Endothelial Cell Activation in Adults with HIV Infection.” 2010. Web. 07 Mar 2021.

Vancouver:

Hileman CO. The Effect of Abacavir on Inflammation and Endothelial Cell Activation in Adults with HIV Infection. [Internet] [Masters thesis]. Case Western Reserve University School of Graduate Studies; 2010. [cited 2021 Mar 07]. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=case1270179884.

Council of Science Editors:

Hileman CO. The Effect of Abacavir on Inflammation and Endothelial Cell Activation in Adults with HIV Infection. [Masters Thesis]. Case Western Reserve University School of Graduate Studies; 2010. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=case1270179884

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