• Wei Zhang, Jing-Jing Yuan, Quan-Cheng Kan, Li-Rong Zhang, Yan-Zi Chang, Zhong-Yu Wang, and Zhi-Song Li.
• Department of Anaesthesia, First Affiliated Hospital, Zhengzhou University, Zhengzhou, China.
• Eur J Anaesthesiol. 2011 Apr 1; 28 (4): 245-50.

Background And ObjectiveFentanyl is metabolised by cytochrome P450 (CYP) 3A4 and CYP3A5. Our previous work demonstrated that the CYP3A4*1G polymorphism significantly affects the post-operative fentanyl analgesic effect in Chinese women undergoing gynaecological surgery. However, whether CYP3A5*3, a frequent single nucleotide polymorphism of CYP3A5 in Chinese people, affects the post-operative analgesic effect of fentanyl is unclear. In this study, we assessed the influence of the CYP3A5*3 polymorphism and the interaction of the CYP3A5*3 and CYP3A4*1G polymorphisms on post-operative fentanyl analgesia in Chinese women undergoing gynaecological surgery.MethodsWe enrolled 203 women scheduled for abdominal total hysterectomy or myomectomy under general anaesthesia. Intravenous fentanyl patient-controlled analgesia was provided post-operatively for adequate analgesia. Pain scores and fentanyl consumption were recorded 24 h post-operatively. Midazolam was used as a probe drug, and CYP3A activity was measured by plasma ratio of 1'-hydroxymidazolam to midazolam 1 h after intravenous administration of 0.1 mg kg-1 midazolam. Blood samples were genotyped for the CYP3A5*3 polymorphism.ResultsThe frequency of the CYP3A5*3 allele was 72.4% in 203 patients. CYP3A activity did not differ among CYP3A5*3 genotypes. Fentanyl consumption 24 h post-operatively was lower with CYP3A5*1/*3 and CYP3A5*3/*3 polymorphisms than with CYP3A5*1/*1, but the differences were not statistically significant. However, combined with CYP3A4*1G polymorphism, post-operative fentanyl consumption at 24 h was significantly lower for the CYP3A5*1/*3 or CYP3A5*3/*3 group than the CYP3A5*1/*1 group.ConclusionCYP3A5*3 is not the main genetic factor contributing to interindividual variation in the post-operative analgesic effect of fentanyl in Chinese women undergoing gynaecological surgery; an interaction between CYP3A5*3 and CYP3A4*1G polymorphisms can significantly influence the post-operative effect.

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