Effect of CYP3A4*1G on the fentanyl consumption for intravenous patient-controlled analgesia after total abdominal hysterectomy in Chinese Han population

Abstract

Clinical investigations into postoperative intravenous patient-controlled analgesia (PCA) have indicated interindividual differences in fentanyl consumption. Cytochrome P450 3A4 (CYP3A4) is the main metabolism enzyme of fentanyl, and single nucleotide polymorphisms within the CYP3A4 gene may contribute to the variability of fentanyl analgesic efficacy. The aim of this study was to investigate whether the most common genetic variation in Chinese, CYP3A4*1G, has an impact on the fentanyl consumption for intravenous PCA in Chinese Han women undergone abdominal total hysterectomy. A total of 79 female patients (American Society of Anesthesiologist physical status I or II) scheduled to undergo elective abdominal total hysterectomy were enrolled. All patients received combined spinal-epidural anaesthesia with bupivacaine. Intravenous fentanyl PCA was provided postoperatively for satisfactory analgesia. The doses of fentanyl consumption were recorded 2, 4, 24 and 48 h after the initiation of PCA postoperatively. Pain at rest and adverse effects were measured with rating scales. CYP3A4*1G was screened by means of direct sequencing and further confirmed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Forty-six patients were GG homozygotes, 27 patients were GA heterozygotes, and six patients were AA homozygotes, respectively. The distribution of the CYP3A4*1G allele was consistent with Hardy-Weinberg equilibrium (P>0·05). At 2 and 4 h, the doses of fentanyl required for patients with GA/AA genotypes were 80·0 (45·0, 112·5) μg and 120·0 (80, 173·8)μg, respectively, and significantly lower than those for GG homozygotes [91·3 (80·0, 125·0) μg and 169·0 (112·5, 226·3) μg, respectively, P<0·05]. There was trend of decreasing fentanyl consumption at 24 and 48h in patients with GA/AA genotypes, relative to GG homozygotes, but the difference was not statistical significant (P>0·05). CYP3A4*1G has an impact on the analgesic effect of fentanyl in Chinese Han subjects. Further validation of our results in a well-powered study would be helpful.