title: Sex difference in formation of propofol metabolites: a replication study.
abstract: 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.
authors.affiliation: Section of Pharmacogenetics, Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Eva
authors.initials: E
authors.lastname: Choong
authors.forename: Irena
authors.initials: I
authors.lastname: Loryan
authors.forename: Marja
authors.initials: M
authors.lastname: Lindqvist
authors.forename: Åsa
authors.initials: Å
authors.lastname: Nordling
authors.forename: Samira
authors.initials: S
authors.lastname: el Bouazzaoui
authors.forename: Ron H
authors.initials: RH
authors.lastname: van Schaik
authors.forename: Inger
authors.initials: I
authors.lastname: Johansson
authors.forename: Jan
authors.initials: J
authors.lastname: Jakobsson
authors.forename: Magnus
authors.initials: M
authors.lastname: Ingelman-Sundberg
mesh_terms: D000328:Adult; D018686:Anesthetics, Intravenous / Q000008:administration & dosage / Q000009:adverse effects*; D019540:Area Under Curve; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics / Q000378:metabolism; D001711:Biotransformation; D003430:Cross-Sectional Studies; D065702:Cytochrome P-450 CYP2B6; D004305:Dose-Response Relationship, Drug; D005260:Female; D014453:Glucuronosyltransferase / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011110:Polymorphism, Genetic; D015742:Propofol / Q000008:administration & dosage / Q000009:adverse effects*; D012737:Sex Factors; D000090264:UDP-Glucuronosyltransferase 1A9
chemical_list: D018686:Anesthetics, Intravenous; C000715591:UGT1A9 protein, human; D001189:Aryl Hydrocarbon Hydroxylases; C585599:CYP2B6 protein, human; D065702:Cytochrome P-450 CYP2B6; D014453:Glucuronosyltransferase; D000090264:UDP-Glucuronosyltransferase 1A9; D015742:Propofol