Department of Anesthesiology, First Affiliated Hospital, Zhengzhou University, Zhengzhou, China.
Eur J Clin Pharmacol. 2010 Jan;66(1):61-6. doi: 10.1007/s00228-009-0726-4. Epub 2009 Sep 26.
To investigate whether the CYP3A4*1G genetic polymorphism contributes to the variability in CYP3A activity and response to fentanyl.
One hundred and forty-three gynecologic patients who were scheduled to undergo abdominal total hysterectomy or myomectomy with general anesthesia were enrolled in this study. Intravenous fentanyl patient-controlled analgesia was provided postoperatively for satisfactory analgesia. The degrees of pain at rest during PCA treatment were assessed with visual analog scale. The fentanyl consumption and occurrence of any adverse effects were recorded in the first 24 h postoperatively. CYP3A activity was measured by plasma 1'-hydroxymidazolam-to-midazolam ratio 1 h after intravenous administration of 0.1 mg/kg midazolam. CYP3A4*1G variant allele was genotyped using the polymerase chain reaction-restriction fragment length polymorphism method.
The frequency of the CYP3A4*1G variant allele was 0.269 in 143 Chinese gynecologic patients. The activity of CYP3A4 in patients homozygous for the *1G/*1G variant (0.34 +/- 0.15) was significantly lower than that in patients bearing the wild-type allele (*1/*1) (0.46 +/- 0.14) or in patients heterozygous for the *1/1G variant (0.46 +/- 0.12) (P < 0.05). The patients with the CYP3A41G/1G genotype needed less fentanyl (227.8 +/- 55.2 microg) to achieve pain control than patients carrying the CYP3A41/1 (381.6 +/- 163.6 microg) and CYP3A41/*1G (371.9 +/- 180.1 microg) genotypes (P < 0.05) during the first 24 h postoperatively. There was no significant difference in incidence of adverse events among the different genotype groups (P > 0.05).
CYP3A4*1G genetic polymorphism decreases CYP3A activity and fentanyl consumption for postoperative pain control.
研究 CYP3A4*1G 基因多态性是否导致 CYP3A 活性的个体差异以及对芬太尼反应的影响。
本研究纳入 143 例行全身麻醉下腹部全子宫切除术或子宫肌瘤切除术的妇科患者。术后采用静脉注射芬太尼患者自控镇痛（PCA）以获得满意的镇痛效果。采用视觉模拟评分法（VAS）评估 PCA 治疗期间静息时的疼痛程度。记录术后 24 小时内的芬太尼消耗量和任何不良反应的发生情况。于静脉注射 0.1mg/kg 咪达唑仑后 1 小时，通过测定血浆 1'-羟咪达唑仑/咪达唑仑比值来评估 CYP3A 活性。采用聚合酶链反应-限制性片段长度多态性方法检测 CYP3A4*1G 变异等位基因。
在 143 例中国妇科患者中，CYP3A4*1G 变异等位基因的频率为 0.269。CYP3A4 基因型为纯合子 *1G/*1G 的患者（0.34±0.15）的 CYP3A4 活性明显低于野生型等位基因（*1/*1）（0.46±0.14）或杂合子 *1/1G（0.46±0.12）（P＜0.05）。与 CYP3A41/1 和 CYP3A41/1G 基因型的患者相比，CYP3A41G/*1G 基因型的患者在术后 24 小时内需要更少的芬太尼（227.8±55.2μg）来达到疼痛控制（P＜0.05）。不同基因型组之间不良反应的发生率无显著差异（P＞0.05）。
CYP3A4*1G 基因多态性降低了 CYP3A 活性和芬太尼用于术后疼痛控制的消耗量。
