Effects of Genetic Polymorphism of CYP2B6 and UGT1A9 and Sex Differences on Pharmacokinetics of Propofol
Effects of Genetic Polymorphism of CYP2B6 and UGT1A9 and Sex Differences on Pharmacokinetics of Propofol
复制标题
CYP2B6和UGT1A9基因多态性及性别差异对异丙酚药代动力学的影响
DOI：
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发表时间：
2015
期刊：
影响因子：
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通讯作者：
T. Tateda
中科院分区：
文献类型：
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作者：
Yuki Kobayashi;M. Yokozuka;Hidetoshi Miyakawa;Minoru Watanabe;T. Kumai;T. Tateda
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 propo‐ fol. Methods: Between June 2009 and May 2011, 94 patients (51 males, 43 females) who underwent respira‐ tory surgery with total intravenous anesthesia were examined. Arterial blood samples were collected immedi‐ ately 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 pharmacokinet‐ ics of propofol and assessed the association between genetic polymorphisms, sex differences, and blood phar‐ macokinetics. Stepwise multiple linear regression analysis was used to detect important factors of pharmacoki‐ netics 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 propo‐ fol 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.
