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Author
Title Paracetamol metabolism in postoperative patients
URL
Publication Date
University/Publisher University College Cork
Abstract Introduction: Despite being available for more than 50 years, there is still much to learn about paracetamol. Postoperative analgesic regimens that maintain good pain control while minimising exposure to opiates are beneficial and paracetamol has had a resurgence in this role since an IV formulation came to market. However there is evidence to suggest currently licensed doses are sub-therapeutic, especially when administered orally or rectally. Higher, unlicensed doses are now being advocated but, prior to this study, there was little evidence of their safety in surgical patients. When assessing drug safety in surgical patients a number of surgery and patient related factors influence results, and these must be considered. Methods: Major and intermediate surgical patients were recruited from two hospitals in Ireland. They were administered IV paracetamol at either 9g or 4g daily doses. In addition they received daily sub therapeutic doses of four other medicines to indicate the activity of their CYP450 enzymes that are involved in paracetamol metabolism. Urine and blood samples were collected to determine paracetamol pharmacokinetics, CYP450 activity, inflammatory cytokine concentration and for evidence of hepatotoxicity. Results: There were 33 patients that participated in the study. There was no evidence of clinically significant hepatotoxicity occurring in any patient during the study period, but there could have been changes following this time. Paracetamol disposition was shown to change, however half-life remained relatively constant. There were a number of changes to the way paracetamol was metabolised following surgery that maintained this rate of elimination. Conclusion: Doses of up to 9g per day given to major surgical patients for up to five days postoperatively produced no evidence of hepatotoxicity. Further research is warranted to determine the clinical utility of these higher doses
Subjects/Keywords Paracetamol; HPLC; Clinical study; Acetaminophen; Drugs – Metabolism; Pharmacokinetics; High performance liquid chromatography; Drugs – Testing
Contributors Kennedy, Julia M.; Byrne, Stephen; Creaton, Geraldine
Language en
Country of Publication ie
Format application/pdf
Record ID handle:10468/573
Repository rian
Date Retrieved
Date Indexed 2018-01-03

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…25 1.3 Changes to drug absorption, distribution, metabolism or excretion due to surgery and Anaesthesia.................................................................................................. 54 1.3.1 Stress response…

…1.3.4 Metabolism .................................................................................................... 82 1.3.5 Excretion ........................................................................................................ 97 1.4…

…Paracetamol Metabolism Study ..........................................................................147 2.1.1 The Patients .................................................................................................148 2.1.2 Study Approval…

…Distribution ..................................................................................................397 x 4.3.2 Metabolism/Clearance ................................................................................ 402 4.3.3 Elimination…

…paracetamol’s activity ....................... 28 Figure 1.2-3 Schematic of prostaglandin H2 synthase (PGHS) metabolism of arachidonic acid to PGH2…

…29 Figure 1.2-4 Metabolism of Paracetamol (Prescott 1996) .................................................. 35 Figure 1.2-5 Paracetamol metabolism shown as structural formulas................................. 36 Figure 1.2-6 All elements of…

…paracetamol metabolism showing all short-lived metabolites with major metabolites underlined in bold ......................................................................... 37 Figure 1.2-7 Glucuronidation pathway in Homo sapiens (Pico et al. 2008)…

…40 Figure 1.2-8 Sulphonation pathway in Homo sapiens (Pico et al. 2008)............................. 41 Figure 1.2-9 Sources and fate of cysteine in paracetamol metabolism. GSH is both a source and consumer of cysteine. Inhibition of…

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