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You searched for subject:(fetal drug exposure). Showing records 1 – 3 of 3 total matches.

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University of Toronto

1. Petrovic, Vanja. Infection-mediated Modulation of Drug Transporters in Pregnancy; Implications for Fetal Drug Exposure.

Degree: PhD, 2015, University of Toronto

Inflammation-mediated changes in the expression and activity of ABC drug-efflux transporters have been shown to alter disposition of their substrates. While ABC transporters play an important role in placenta by limiting transplacental transfer of xenobiotics, little is known about the impact of inflammatory stimuli on these transporters during pregnancy. Using animal models, we investigated the impact of infection-induced acute inflammation on the expression of P-GP (ABCB1), BCRP (ABCG2) and MRP1-3 (ABCC1-3) efflux transporters, as well as several OATP (SLCO) uptake transporters in livers and placentas of pregnant rats. We explored how changes in placental transporter levels impact fetal drug exposure. Our studies demonstrated that endotoxin and polyinosinic/polycytidylic acid [poly(I:C)] induce pro-inflammatory cytokine levels in plasma of pregnant rats and generally downregulate mRNA and protein expression of several important hepatic and placental drug uptake and efflux transporters. Moreover, these changes were associated with alterations in maternal and fetal drug disposition of clinically relevant substrates. Downregulation of Bcrp was associated with a pronounced increase in fetal accumulation of its substrate, glyburide in endotoxin-treated rats. Significantly increased maternal exposure to P-gp substrate, lopinavir was observed in poly(I:C)-treated rats, with evidence of altered placental transfer and fetal disposition. Additionally, bile acids, which are endogenous substrates of many affected hepatic transporters, were significantly increased in maternal plasma of poly(I:C)-treated rats. While the observed differences could also be attributed to inflammation-induced variability in drug metabolism and protein binding, our findings provide evidence that decreased expression of efflux transporters significantly contributes to modulation of materno-fetal transport and disposition. Lastly, translational studies utilizing human placenta demonstrated similar impact of infections on expression of drug transporters such as BCRP and OATP2B1, indicating the need for a closer clinical investigation of inflammation-mediated changes in transporter expression and the possible impact on maternal drug disposition and fetal drug exposure.

2017-06-08 00:00:00

Advisors/Committee Members: Piquette-Miller, Micheline, Pharmaceutical Sciences.

Subjects/Keywords: Drug transporters; Fetal drug exposure; Infection; Inflammation; Placenta; Pregnancy; 0419

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

APA (6th Edition):

Petrovic, V. (2015). Infection-mediated Modulation of Drug Transporters in Pregnancy; Implications for Fetal Drug Exposure. (Doctoral Dissertation). University of Toronto. Retrieved from http://hdl.handle.net/1807/77511

Chicago Manual of Style (16th Edition):

Petrovic, Vanja. “Infection-mediated Modulation of Drug Transporters in Pregnancy; Implications for Fetal Drug Exposure.” 2015. Doctoral Dissertation, University of Toronto. Accessed April 15, 2021. http://hdl.handle.net/1807/77511.

MLA Handbook (7th Edition):

Petrovic, Vanja. “Infection-mediated Modulation of Drug Transporters in Pregnancy; Implications for Fetal Drug Exposure.” 2015. Web. 15 Apr 2021.

Vancouver:

Petrovic V. Infection-mediated Modulation of Drug Transporters in Pregnancy; Implications for Fetal Drug Exposure. [Internet] [Doctoral dissertation]. University of Toronto; 2015. [cited 2021 Apr 15]. Available from: http://hdl.handle.net/1807/77511.

Council of Science Editors:

Petrovic V. Infection-mediated Modulation of Drug Transporters in Pregnancy; Implications for Fetal Drug Exposure. [Doctoral Dissertation]. University of Toronto; 2015. Available from: http://hdl.handle.net/1807/77511


University of Washington

2. Dorfman, Elizabeth Howard. Translational Research in Obstetric Pharmacology: Historical Trends, Prenatal Pharmacogenomics, and an Opportunistic Study of Placental ABCG2 and Fetal Glyburide Exposure.

Degree: PhD, 2015, University of Washington

This dissertation is principally comprised of three distinct but related projects. The first is an assessment of the quantity and nature of obstetric pharmacology clinical trials conducted in the past decade, as well as a comparison of these trials to non-obstetric trials, in order to identify whether the challenges and complexities of conducting research in this field are reflected in the aggregate study data available through ClinicalTrials.gov. The analysis identified several significant differences between obstetric and non-obstetric trials, which have implications for program planning and funding needs. Second is an overview of the ways in which the fetal genome may be informative of fetal outcomes with regard to medication and other chemical exposures during pregnancy, and the attendant research prioritization of this area and clinical testing opportunities made possible by non-invasive prenatal genetic tests that utilize cell-free fetal DNA in a pregnant woman’s blood. Finally, an opportunistic clinical study was conducted, assessing whether fetal genotype for the placental efflux transporter breast cancer resistance protein (BCRP, ABCG2) is predictive of relative fetal exposure to the oral hypoglycemic agent glyburide, which is used, off-label as an alternative to insulin, to treat gestational diabetes. The results of the study showed no association between fetal ABCG2 Q141K genotype and relative glyburide exposure at term, which was unexpected given the extensive, albeit indirect, supporting evidence that formed the basis of the initial hypothesis. This result has clinical implications related to the optimal use of glyburide to treat gestational diabetes, and also underscores the complexity of drug disposition during pregnancy and the need to study pregnant women directly. Advisors/Committee Members: Thummel, Kenneth E (advisor).

Subjects/Keywords: ABCG2; breast cancer resistance protein; fetal drug exposure; glyburide; obstetric pharmacology; placental drug transport; Genetics; Pharmacology; Obstetrics and gynecology; public health genetics

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

APA (6th Edition):

Dorfman, E. H. (2015). Translational Research in Obstetric Pharmacology: Historical Trends, Prenatal Pharmacogenomics, and an Opportunistic Study of Placental ABCG2 and Fetal Glyburide Exposure. (Doctoral Dissertation). University of Washington. Retrieved from http://hdl.handle.net/1773/34161

Chicago Manual of Style (16th Edition):

Dorfman, Elizabeth Howard. “Translational Research in Obstetric Pharmacology: Historical Trends, Prenatal Pharmacogenomics, and an Opportunistic Study of Placental ABCG2 and Fetal Glyburide Exposure.” 2015. Doctoral Dissertation, University of Washington. Accessed April 15, 2021. http://hdl.handle.net/1773/34161.

MLA Handbook (7th Edition):

Dorfman, Elizabeth Howard. “Translational Research in Obstetric Pharmacology: Historical Trends, Prenatal Pharmacogenomics, and an Opportunistic Study of Placental ABCG2 and Fetal Glyburide Exposure.” 2015. Web. 15 Apr 2021.

Vancouver:

Dorfman EH. Translational Research in Obstetric Pharmacology: Historical Trends, Prenatal Pharmacogenomics, and an Opportunistic Study of Placental ABCG2 and Fetal Glyburide Exposure. [Internet] [Doctoral dissertation]. University of Washington; 2015. [cited 2021 Apr 15]. Available from: http://hdl.handle.net/1773/34161.

Council of Science Editors:

Dorfman EH. Translational Research in Obstetric Pharmacology: Historical Trends, Prenatal Pharmacogenomics, and an Opportunistic Study of Placental ABCG2 and Fetal Glyburide Exposure. [Doctoral Dissertation]. University of Washington; 2015. Available from: http://hdl.handle.net/1773/34161


University of Florida

3. Swanson, Douglas James, 1964-. The Effects of chronic prenatal ethanol exposure on CNS cholinergic development.

Degree: 1994, University of Florida

Subjects/Keywords: Research ( mesh ); Disease Models, Animal ( mesh ); Fetal Alcohol Syndrome  – etiology ( mesh ); Fetal Alcohol Syndrome  – chemically induced ( mesh ); Ethanol  – toxicity ( mesh ); Ethanol  – pharmacology ( mesh ); Prenatal Exposure Delayed Effects ( mesh ); Purkinje Cells  – drug effects ( mesh ); Purkinje Cells  – growth and development ( mesh ); Cholinergic Fibers  – drug effects ( mesh ); Cholinergic Fibers  – growth and development ( mesh ); Rats ( mesh ); Chick Embryo ( mesh ); Department of Neuroscience thesis Ph.D ( mesh )

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

APA (6th Edition):

Swanson, Douglas James, 1. (1994). The Effects of chronic prenatal ethanol exposure on CNS cholinergic development. (Thesis). University of Florida. Retrieved from https://ufdc.ufl.edu/AA00067426

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

Chicago Manual of Style (16th Edition):

Swanson, Douglas James, 1964-. “The Effects of chronic prenatal ethanol exposure on CNS cholinergic development.” 1994. Thesis, University of Florida. Accessed April 15, 2021. https://ufdc.ufl.edu/AA00067426.

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

MLA Handbook (7th Edition):

Swanson, Douglas James, 1964-. “The Effects of chronic prenatal ethanol exposure on CNS cholinergic development.” 1994. Web. 15 Apr 2021.

Vancouver:

Swanson, Douglas James 1. The Effects of chronic prenatal ethanol exposure on CNS cholinergic development. [Internet] [Thesis]. University of Florida; 1994. [cited 2021 Apr 15]. Available from: https://ufdc.ufl.edu/AA00067426.

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

Council of Science Editors:

Swanson, Douglas James 1. The Effects of chronic prenatal ethanol exposure on CNS cholinergic development. [Thesis]. University of Florida; 1994. Available from: https://ufdc.ufl.edu/AA00067426

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

.