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

通过包括克拉霉素在内的标准三联药物方案抑制 CYP3A 活性，以根除幽门螺杆菌感染

基本信息

批准号：
14572166
负责人：
ECHIZEN Hirotoshi
金额：
$ 1.98万
依托单位：
Meiji Pharmaceutical University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2004
项目状态：
已结题

项目摘要

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

兰索拉唑、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，我们研究了标准的克拉霉素三联疗法是否会在H Pylori阳性患者中引起临床相关的细胞色素P450(CYP)3A抑制。将20例幽门螺杆菌阳性的消化性溃疡患者随机分为两组，一组给予克拉霉素200 mg、兰索拉唑30 mg、阿莫西林750 mg，另一组给予克拉霉素400 mg、兰索拉唑30 mg、阿莫西林750 mg。10名健康对照受试者接受兰索拉唑30 mg和阿莫西林750 mg。所有受试者在服药前(第0天)和服药后第7天采集尿样，测定尿6-β-羟基皮质醇和皮质醇，并采集中点血浆测定皮质醇。用部分c-…法测定体内细胞色素P3A活性更多的皮质醇清除6-羟基皮质醇(CL_&lt；cortisol&gt；→_6β_&lt；-hydroxycortisol&gt；).β每天服用400 mg和800 mg克拉霉素根除幽门螺杆菌的患者CL_&lt；cortisol&gt；→_6β_&lt；-hydroxycortisol&gt；，分别下降了39%(P&lt；0.05)和68%(P&lt；0.05)。相比之下，对照组受试者的CL_&lt；cortisol&gt；→_6β_&lt；-hydroxycortisol&gt；.没有明显变化兰索拉唑的平均3小时血药浓度与克拉霉素的剂量成正比(P&lt；0.05与对照组相比)。结论克拉霉素、阿莫西林和兰索拉唑联合7d根除幽门螺杆菌可显著抑制体内细胞色素P3A的活性。尽管由此导致的兰索拉唑血药浓度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，必须注意药物可能与同时使用的细胞色素P3A底物(S)相互作用。较少

项目成果

期刊论文数量（24）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

The in vivo effects of sho-saiko-to, a traditional Chinese herbal medicine, on two cytochrome P450 enzymes (1A2 and 3A) and xanthine oxidase in man.

传统中草药升斋藤对人体两种细胞色素 P450 酶（1A2 和 3A）和黄嘌呤氧化酶的体内影响。

DOI：
发表时间：
2003
期刊：
J Pharm Pharmacol 55
影响因子：
0
作者：
Junji Saruwatari;Kazuko Nakagawa;Junichi Shindo;Shinobu Nachi;Hitotoshi Echizen;Takashi Ishizaki
通讯作者：
Takashi Ishizaki

医薬品の相互作用:その虚像と実像・科学的実証を求めて

药物相互作用：寻找虚拟和真实图像以及科学证据