{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,28]],"date-time":"2026-03-28T18:56:28Z","timestamp":1774724188711,"version":"3.50.1"},"reference-count":0,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2002,7,3]],"date-time":"2002-07-03T00:00:00Z","timestamp":1025654400000},"content-version":"vor","delay-in-days":2,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clin Pharma and Therapeutics"],"published-print":{"date-parts":[[2002,7]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>A 7\u2010day triple therapy with lansoprazole, amoxicillin (INN, amoxicilline), and clarithromycin is widely used for eradication of <jats:italic>Helicobacter pylori<\/jats:italic>. Because clarithromycin is a potent inhibitor of cytochrome P450 (CYP) 3A, we investigatedwhether the standard triple therapy with clarithromycin would elicit clinically relevant CYP3A inhibition and alter CYP3A\u2010mediated lansoprazole disposition in <jats:italic>H pylori<\/jats:italic>\u2010positive patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Twenty <jats:italic>H pylori<\/jats:italic>\u2010positive patients with peptic ulcer disease were randomly assigned to 2 groups: One group received 200 mg clarithromycin, 30 mg lansoprazole, and 750 mg amoxicillin at 8 am and 8 pm for 7 days; the other group received 400 mg clarithromycin, 30 mg lansoprazole, and 750 mg amoxicillin at 8 am and 8 pm for 7 days. Ten healthy control subjects received 30 mg lansoprazole and 750 mg amoxicillin at 8 amand 8 pm for 7 days but did not receive clarithromycin. Urine samples were collected for 3 hours (from 8 am to 11 am) for urinary 6\u03b2\u2010hydroxycortisol and cortisol assay, and midpoint (at 9:30 am) 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 cortisol clearance by means of the formation of 6\u03b2\u2010hydroxycortisol (CL<jats:sub>cortisol\u21926\u03b2\u2010hydroxycortisol<\/jats:sub>) and the urinary 6\u03b2\u2010hydroxycortisol\/cortisol ratio. Additional plasma samples for lansoprazole, 5\u2010hydroxylansoprazole, and lansoprazole sulfone assay were obtained at 11 am on day 7.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The groups of patients given 400 and 800 mg\/day clarithromycin for <jats:italic>H pylori<\/jats:italic> eradication therapy showed 39% (from 2.20 \u00b1 1.29 to 1.35 \u00b1 0.88 mL\/min [day 0 versus 7, mean \u00b1 SD]; <jats:italic>P<\/jats:italic> &lt; .05) and 68%(2.40 \u00b1 1.22 to 0.76 \u00b1 0.51 mL\/min; <jats:italic>P<\/jats:italic> &lt; .05) reductions in CL<jats:sub>cortisol\u21926\u03b2\u2010hydroxycortisol<\/jats:sub>, respectively. In contrast, the control subjects given lansoprazole and amoxicillin without clarithromycin showed no significant changes in CL<jats:sub>cortisol\u21926\u03b2\u2010hydroxycortisol<\/jats:sub>. The urinary 6\u03b2\u2010hydroxycortisol\/cortisol ratio also decreased significantly (<jats:italic>P<\/jats:italic> &lt; .05) in the patient groups but not in the control subjects. The mean 3\u2010hour plasma lansoprazole levels elevated in proportion to the doses of clarithromycin: 385 \u00b1 338 ng\/mL for the control subjects, 696 \u00b1 797 ng\/mL for the <jats:italic>H pylori<\/jats:italic>\u2010positive patients given 400 mg\/day clarithromycin, and 947 \u00b1 806 ng\/mL for the <jats:italic>H pylori<\/jats:italic>\u2010positive patients given 800 mg\/day clarithromycin (<jats:italic>P<\/jats:italic> &lt; .05 versus the control subjects). No significant differences were observed among the groups in the mean plasma ratios of 5\u2010hydroxylansoprazole or lansoprazole sulfone to lansoprazole.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p><jats:italic>The 7\u2010day H pylori<\/jats:italic> 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 beneficialfor <jats:italic>H pylori<\/jats:italic> eradication, caution must be exercised for possible drug interaction with a concomitantly administered CYP3A substrate (s) in patients undergoing <jats:italic>H pylori<\/jats:italic> eradication therapy with clarithromycin, amoxicillin, and lansoprazole.<\/jats:p><jats:p><jats:italic>Clinical Pharmacology &amp; Therapeutics<\/jats:italic> (2002) <jats:bold>72<\/jats:bold>, 33\u201343; doi: <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1067\/mcp.2002.125559\">10.1067\/mcp.2002.125559<\/jats:ext-link><\/jats:p><\/jats:sec>","DOI":"10.1067\/mcp.2002.125559","type":"journal-article","created":{"date-parts":[[2002,10,9]],"date-time":"2002-10-09T21:24:11Z","timestamp":1034198651000},"page":"33-43","source":"Crossref","is-referenced-by-count":45,"title":["Dose\u2010dependent inhibition of CYP3A activity by clarithromycin during <i>Helicobacter pylori<\/i> eradication therapy assessed by changes in plasma lansoprazole levels and partial cortisol clearance to 6\u03b2\u2010hydroxycortisol"],"prefix":"10.1111","volume":"72","author":[{"given":"Hideki","family":"Ushiama","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine, Daisan Hospital Jikei University School of Medicine"},{"name":"Department of Pharmacotherapy, Meiji Pharmaceutical University  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hirotoshi","family":"Echizen","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Daisan Hospital Jikei University School of Medicine"},{"name":"Department of Pharmacotherapy, Meiji Pharmaceutical University  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shinobu","family":"Nachi","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Daisan Hospital Jikei University School of Medicine"},{"name":"Department of Pharmacotherapy, Meiji Pharmaceutical University  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Akihiro","family":"Ohnishi","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Daisan Hospital Jikei University School of Medicine"},{"name":"Department of Pharmacotherapy, Meiji Pharmaceutical University  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2002,7,3]]},"container-title":["Clinical Pharmacology &amp; Therapeutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1067\/mcp.2002.125559","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,18]],"date-time":"2023-11-18T10:34:53Z","timestamp":1700303693000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/10.1067\/mcp.2002.125559"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2002,7]]},"references-count":0,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2002,7]]}},"alternative-id":["10.1067\/mcp.2002.125559"],"URL":"https:\/\/doi.org\/10.1067\/mcp.2002.125559","archive":["Portico"],"relation":{},"ISSN":["0009-9236","1532-6535"],"issn-type":[{"value":"0009-9236","type":"print"},{"value":"1532-6535","type":"electronic"}],"subject":[],"published":{"date-parts":[[2002,7]]}}}