Paracetamol metabolism in postoperative patients

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dc.contributor.advisor Kennedy, Julia M.
dc.contributor.advisor Byrne, Stephen
dc.contributor.advisor Creaton, Geraldine Murphy, Philip Gerard MacHale 2012-05-02T13:09:35Z 2012-05-02T13:09:35Z 2012-01 2012-01-19
dc.identifier.citation Murphy, P.G., 2012. Paracetamol metabolism in postoperative patients. PhD Thesis, University College Cork. en
dc.description.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 en
dc.format.mimetype application/pdf en
dc.language.iso en en
dc.publisher University College Cork en
dc.rights © 2012, Philip Gerard MacHale Murphy en
dc.rights.uri en
dc.subject Paracetamol en
dc.subject HPLC en
dc.subject Clinical study en
dc.subject.lcsh Acetaminophen en
dc.subject.lcsh Drugs--Metabolism en
dc.subject.lcsh Pharmacokinetics en
dc.subject.lcsh High performance liquid chromatography en
dc.subject.lcsh Drugs--Testing en
dc.title Paracetamol metabolism in postoperative patients en
dc.type Doctoral thesis en
dc.type.qualificationlevel Doctoral en
dc.type.qualificationname PhD (Medicine & Health) en
dc.internal.availability Full text available en
dc.description.version Accepted Version en
dc.description.status Not peer reviewed en Pharmacy en

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© 2012, Philip Gerard MacHale Murphy Except where otherwise noted, this item's license is described as © 2012, Philip Gerard MacHale Murphy
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