Impact of CYP3A4*1G polymorphism on metabolism of fentanyl in Chinese patients undergoing lower abdominal surgery

Abstract

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 The frequency of CYP3A4*1G variant allele was 0.227 (80/352, 95% CI 0.165, 0.289) in these patients. After grouping according to the genotype of CYP3A4*1G, plasma fentanyl concentration in the *1/*1 variant (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). Patients in the *1G/*1G group (247.1 ± 73.2 μg) consumed significantly less fentanyl than that in either the wild-type group (395.0 ± 138.5 μg) or the *1/*1G group (359.8 ± 120.2 μg) ( 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 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.