2004 Fiscal Year Final Research Report Summary
Inhibition of CYP3A activity by a standard triple drug regimen including clarithromycin for eradication of Helicobacter pylori infection
| Project/Area Number |
14572166
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
応用薬理学・医療系薬学
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| Research Institution | Meiji Pharmaceutical University |
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Principal Investigator |
ECHIZEN Hirotoshi Meiji Pharmaceutical University, Department of Pharmacotherapy, Professor, 薬学部, 教授 (00191924)
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| Co-Investigator(Kenkyū-buntansha) |
OHNISHI Akihiro Jikei Medical School, Department of Internal Medicine, Associate Professor, 医学部, 助教授 (00194225)
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| Project Period (FY) |
2002 – 2004
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| Keywords | clarithromycin / cytochrome P450 / Helicobacter pylori / drug interaction / lansoprazole / cortisol / partial metabolic clearance / 6β-hydroxycortisol |
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| Research Abstract |
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
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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
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