Inhibition of CYP3A activity by a standard triple drug regimen including clarithromycin for eradication of Helicobacter pylori infection

兰索拉唑、阿莫西林（INN、阿莫西林）和克拉霉素三联疗法被广泛用于根除幽门螺杆菌。由于克拉霉素是细胞色素P450 (CYP) 3A的有效抑制剂，我们研究了克拉霉素标准三联疗法是否会在幽门螺杆菌阳性患者中引起临床相关的CYP3A抑制。20例幽门螺杆菌阳性消化性溃疡患者随机分为两组：一组给予200 mg克拉霉素、30 mg兰索拉唑和750 mg阿莫西林；另一组服用400毫克克拉霉素、30毫克兰索拉唑和750毫克阿莫西林。10名健康对照者分别给予兰索拉唑30 mg和阿莫西林750 mg。在药物治疗前（第0天）和第7天采集所有受试者尿液样本3小时用于尿6β-羟基皮质醇和皮质醇测定，并采集血浆中点样本用于皮质醇测定。对6β-羟基皮质醇（CL_<皮质醇>→_6β_<-羟基皮质醇>）有更多的ortisol清除率。400 mg/d和800 mg/d克拉霉素组幽门螺杆菌根除治疗CL_<皮质醇>→_6β_<-羟基皮质醇>分别降低39% （P< 0.05）和68% （P< 0.05）。对照组CL_<皮质醇>→_6β_<-羟基皮质醇>无明显变化。平均3小时血浆兰索拉唑水平与克拉霉素剂量成比例升高（与对照组相比P< 0.05）。由此得出结论，克拉霉素、阿莫西林和兰索拉唑7天的幽门螺杆菌根除治疗可能会引起体内CYP3A活性的实质性抑制。尽管血浆兰索拉唑浓度的升高可能有利于根除幽门螺杆菌，但在接受克拉霉素、阿莫西林和兰索拉唑根除幽门螺杆菌治疗的患者中，必须谨慎使用可能与同时给予CYP3A底物的药物相互作用。少

A triple therapy with lansoprazole, amoxicillin (INN, amoxicilline), and clarithromycin is widely used for eradication of Helicobacter pylori. Because clarithromycin is a potent inhibitor of cytochrome P450 (CYP) 3A, we investigated whether the standard triple therapy with clarithromycin would elicit clinically relevant CYP3A inhibition in H pylori-positive patients. Twenty H pylori-positive patients with peptic ulcer disease were randomly assigned to 2 groups : One group received 200 mg clarithromycin, 30 mg lansoprazole, and 750 mg amoxicillin ; the other group received 400 mg clarithromycin, 30 mg lansoprazole, and 750 mg amoxicillin. Ten healthy control subjects received 30 mg lansoprazole and 750 mg amoxicillin. Urine samples were collected for 3 hours for urinary 6β-hydroxycortisol and cortisol assay, and midpoint plasma samples for cortisol assay were obtained from all participants before the drug therapy (day 0) and on day 7. In vivo CYP3A activity was assessed by the partial c … More ortisol clearance to 6β-hydroxycortisol (CL_<cortisol>→_6β_<-hydroxycortisol>). The groups of patients given 400 and 800 mg/day clarithromycin for H pylori eradication therapy showed 39% (P<.05) and 68% (P<.05) reductions in CL_<cortisol>→_6β_<-hydroxycortisol>, respectively. In contrast, the control subjects showed no significant changes in CL_<cortisol>→_6β_<-hydroxycortisol>. The mean 3-hour plasma lansoprazole levels elevated in proportion to the doses of clarithromycin (P<.05 versus the control subjects). It was condluded that the 7-day H pylori eradication therapy with clarithromycin, amoxicillin, and lansoprazole may elicit substantial inhibition of in vivo CYP3A activity. Although resultant elevations in plasma lansoprazole concentrations may be beneficial for H pylori eradication, caution must be exercised for possible drug interaction with a concomitantly administered CYP3A substrate (s) in patients undergoing H pylori eradication therapy with clarithromycin, amoxicillin, and lansoprazole. Less