Background: Genetic polymorphisms of metabolic enzymes, as well as a patient’s sex, age, and individual susceptibility, affect the pharmacokinetics of propofol. Several reports show that polymorphisms of metabolic enzymes of propofol affect loss of consciousness during propofol anesthesia. We investigated whether genetic polymorphisms of the liver cytochrome P450 2B6 (CYP2B6), the main metabolic enzyme for propofol, and UDP-glucuronosyltransferase 1A9 (UGT1A9), as well as sex differences, affect the pharmacokinetics of propofol.
Methods: Between June 2009 and May 2011, 94 patients (51 males, 43 females) who underwent respiratory surgery with total intravenous anesthesia were examined. Arterial blood samples were collected immediately or 5, 10, 20, 30 and 60 min after the termination of propofol infusion for the determination of the propofol blood concentrations and genetic polymorphisms of CYP2B6 and UGT1A9. We analyzed blood pharmacokinetics of propofol and assessed the association between genetic polymorphisms, sex differences, and blood pharmacokinetics. Stepwise multiple linear regression analysis was used to detect important factors of pharmacokinetics of propofol.
Results: Although C₀ (the blood concentrations of propofol immediately after the termination of propofol infusion) rose for the T/T mutation in CYP2B6, there were no significant differences in changes of blood propofol concentrations after the termination of drug infusion and in waking times for both genetic polymorphisms. C₀ was significantly higher in females than in males (1.7: 1.4 μg/mL, female: male, P=0.015) and the rate of decline in the blood propofol concentration from C₀ to C₅ was faster in females than in males (67: 60%, P=0.015). Stepwise multiple regression analysis revealed that sex (B = 0.32, P = 0.01) was a contributor to C₀ (R = 0.27, P = 0.01).
Conclusions: We suggest that differences between females and males for C₀ and the rate of decline in the blood propofol concentration may cause individual differences in both sensitivity and recovery of consciousness from propofol anesthesia. We conclude that polymorphisms of CYP2B6, but not UGT1A, and sex differences affect the pharmacokinetics of propofol.