Impact Of CYP3A4*1G Polymorphism On Metabolism Of Fentanyl In Chinese Patients Undergoing Lower Abdominal Surgery

Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science &Technology, Wuhan, PR China,430030 Purpose: This study aimed to investigate the impact of CYP3A4*1G genetic polymorphism on metabolism of fentanyl in Chinese patients undergoing lower abdominal surgery.Methods: 176 patients receiving elective lower abdominal surgery under general anesthesia were recruited into this study. Genotyping of CYP3A4*1G was carried out by direct sequencing. The plasma fentanyl concentration was detected 30 min after anesthesia induction by high performance liquid chromatography-ultraviolet ray (HPLC-UV). The visual analog scale (VAS) was used for pain evaluation at rest during patient-controlled analgesia (PCA) treatment 0 h, 12 h and 24 h after operation. PCA fentanyl consumption and adverse effects were recorded during the first 24 h after surgery.Results: All the subjects were divided into three groups based on the results of genotyping: 103 with wild-type homozygote (*1/*1), 66 with heterozygote (*1/*1G), and 7 with mutant homozygote (*1G/*1G). The frequency of CYP3A4*1G variant allele was 0.227(80/352, 95% CI: 0.165, 0.289). The plasma fentanyl concentration 30 min after induction was 14.9±8.3 ng/ml (95%CI: 13.7, 16.2; range: 2.5-44.7 ng/ml) among all patients. Plasma fentanyl concentration in the wild-type group (12.8±6.5 ng/ml) was significantly lower than that in the *1/*1G group (16.8±9.0 ng/ml, P<0.01) and the *1G/*1G group (28.1±9.5 ng/ml, P<0.01). The average fentanyl consumption was 375.9±133.0μg (95%CI: 356.1, 395.7; range: 160.0-890.0μg) in the first 24 h postoperatively among all patients. No significant differences in the scores of VAS were noted between the three groups (P>0.05). While to achieve similar degrees of pain control, patients in the *1G/*1G group (247.1±73.2μg) consumed significantly less fentanyl than that in either the wild-type group (395.0±138.5μg) or the *1/*1G group (359.8±120.2μg) (P<0.01). There was a significant correlation between plasma fentanyl concentration and PCA fentanyl consumption (r=-0.552, P<0.001).Conclusions: CYP3A4*1G polymorphism is notable related to the pharmacokinetics of fentanyl, and patients with CYP3A4*1G variant A allele have a lower metabolic rate of fentanyl. The specific CYP3A4*1G polymorphism may predict the individual requirement of fentanyl.