| The recovery time-course of CYP3A after induction by St John's wort administration. | |
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MedLine Citation:
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PMID: 18294328 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: St John's wort causes the induction of CYP3A. Little is known about how long the effect remains after cessation of St John's wort. WHAT THIS STUDY ADDS: The in vivo CYP3A activity returns progressively to the basal level approximately 1 week after cessation of St John's wort administration AIMS: To examine the recovery time course of CYP3A after enzyme induction by St John's wort administration. METHODS: The subjects were 12 healthy men, aged 20-33 years. On the first day, they received an oral dose of midazolam 5 mg without St John's wort (day -14). From the next day, they took St John's wort for 14 days. On the last day of St John's wort treatment (day 0) and 3 and 7 days after completion of St John's wort treatment (days 3 and 7), they received the same dose of midazolam. On each day, blood samples were obtained until 8 h after midazolam administration. Plasma concentrations of midazolam were measured by HPLC. Pharmacokinetic parameters of midazolam were determined using noncompartmental analysis. RESULTS: Apparent oral clearance of midazolam was significantly increased after St John's wort administration from 65.3 +/- 8.4 l h(-1) (day -14) to 86.8 +/- 17.3 l h(-1) (day 0). It returned to the control level 7 days after the completion of St John's wort (day 7, 59.7 +/- 3.8 l h(-1)). No significant difference in the elimination half-life between the four periods of the study was observed. The changes in apparent oral clearance after St John's wort discontinuation indicated that CYP3A activity recovers from enzyme induction with an estimated half-life of 46.2 h. CONCLUSIONS: CYP3A activity induced by St John's wort administration progressively returns to the basal level after approximately 1 week. This finding may provide useful information to avoid clinically significant interactions of St John's wort with CYP3A substrates. |
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Authors:
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Hiromitsu Imai; Tsutomu Kotegawa; Kimiko Tsutsumi; Takuya Morimoto; Nobuoki Eshima; Shigeyuki Nakano; Kyoichi Ohashi |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2008-02-20 |
Journal Detail:
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Title: British journal of clinical pharmacology Volume: 65 ISSN: 1365-2125 ISO Abbreviation: Br J Clin Pharmacol Publication Date: 2008 May |
Date Detail:
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Created Date: 2008-04-23 Completed Date: 2008-07-23 Revised Date: 2012-09-10 |
Medline Journal Info:
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Nlm Unique ID: 7503323 Medline TA: Br J Clin Pharmacol Country: England |
Other Details:
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Languages: eng Pagination: 701-7 Citation Subset: IM |
Affiliation:
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Department of Clinical Pharmacology and Therapeutics, Oita University Faculty of Medicine, Oita, Japan. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adult Cytochrome P-450 CYP3A / metabolism* GABA Modulators / pharmacokinetics* Humans Hypericum* Male Midazolam / pharmacokinetics* Plant Extracts / administration & dosage, pharmacology* Time Factors |
| Chemical | |
Reg. No./Substance:
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0/GABA Modulators; 0/Plant Extracts; 59467-70-8/Midazolam; EC 1.14.14.1/Cytochrome P-450 CYP3A |
| Comments/Corrections | |
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