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

2011; Elsevier BV; Volume: 412; Issue: 9-10 Linguagem: Inglês

10.1016/j.cca.2010.12.038

1873-3492

Ruimei Yuan, Xianwei Zhang, Qian Deng, Yuan Wu, Guifang Xiang,

Diet and metabolism studies

This study aimed to investigate the impact of CYP3A4*1G genetic polymorphism on metabolism of fentanyl in Chinese patients undergoing lower abdominal surgery.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.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).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.