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Sex difference in formation of propofol metabolites: a replication study
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences. Karolinska Institutet, Yerevan State Medical University. (Translational PKPD)ORCID iD: 0000-0002-1557-4416
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2013 (English)In: Basic & Clinical Pharmacology & Toxicology, ISSN 1742-7835, E-ISSN 1742-7843, Vol. 113, no 2, 126-131 p.Article in journal (Refereed) Published
Abstract [en]

Women recover faster from propofol anaesthesia and have been described to have a higher incidence of awareness during surgery, compared to men - an effect that may be inherent in sex differences in propofol metabolism. In an observational study, 98 ASA I-II patients treated with continuous propofol infusion were recruited. The associations between sex and CYP2B6 and UGT1A9 polymorphisms with dose- and weight-adjusted area under the total plasma level time curves (AUC) for propofol, and its metabolites propofol glucuronide (PG), 4-hydroxypropofol (OHP) and hydroxyl glucuronide metabolites 4-hydroxypropofol-1-O-β-D-glucuronide (Q1G) and 4-hydroxypropofol-4-O-β-D-glucuronide (Q4G), were analysed. Significantly higher AUC of PG (1.3 times, p = 0.03), Q1G (2.9 times, p < 0.001), Q4G (2.4 times, p < 0.01) and OHP (4.6 times, p = 0.01) were found in women (n = 53) than in men (n = 45) after intravenous infusion of propofol using target-controlled infusion system. There was, however, no significant impact of gene polymorphisms on propofol biotransformation. The results, which are supported by a previous pilot study using a propofol bolus dose, suggest that, compared to men, more rapid propofol metabolism may occur in women - a factor that may contribute to the mentioned differences in the efficacy of propofol anaesthesia between male and female patients.

Place, publisher, year, edition, pages
2013. Vol. 113, no 2, 126-131 p.
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Medical and Health Sciences
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URN: urn:nbn:se:uu:diva-222232DOI: 10.1111/bcpt.12070PubMedID: 23527701OAI: oai:DiVA.org:uu-222232DiVA: diva2:711018
Available from: 2014-04-09 Created: 2014-04-09 Last updated: 2017-12-05Bibliographically approved

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