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Sex difference in formation of propofol metabolites : a replication study

Choong, Eva (author)
Karolinska Institutet
Loryan, Irena, 1977- (author)
Uppsala universitet,Institutionen för farmaceutisk biovetenskap,Karolinska Institutet, Yerevan State Medical University,Translational PKPD
Lindqvist, Marja (author)
Karolinska Institutet
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Nordling, Åsa (author)
el Bouazzaoui, Samira (author)
van Schaik, Ron H (author)
Johansson, Inger (author)
Karolinska Institutet
Jakobsson, Jan (author)
Karolinska Institutet
Ingelman-Sundberg, Magnus (author)
Karolinska Institutet
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 (creator_code:org_t)
2013-05-20
2013
English.
In: Basic & Clinical Pharmacology & Toxicology. - : Wiley. - 1742-7835 .- 1742-7843. ; 113:2, s. 126-131
  • Journal article (peer-reviewed)
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  • 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.

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