In vitro inhibitory effects of Wen-pi-tang-Hab-Wu-ling-san on human cytochrome P450 isoforms

Title
In vitro inhibitory effects of Wen-pi-tang-Hab-Wu-ling-san on human cytochrome P450 isoforms
Author(s)
임미선H. W. Lee[H. W. Lee]D. W. Kim[D. W. Kim]P. B. Phapale[P. B. Phapale]J. Park[J. Park]J. J. Seo[J. J. Seo]K. M. Park[K. M. Park]Y. -K. Park[Y. -K. Park]Y. -R. Yoon[Y. -R. Yoon]
Keywords
HUMAN LIVER-MICROSOMES; PERFORMANCE LIQUID-CHROMATOGRAPHY; HERB-DRUG-INTERACTIONS; TANDEM MASS-SPECTROMETRY; TOLBUTAMIDE HYDROXYLATION; OXIDATIVE-METABOLISM; HUMAN PLASMA; HUMAN CYP1A2; DEXTROMETHORPHAN; OMEPRAZOLE
Issue Date
201108
Publisher
WILEY-BLACKWELL
Citation
JOURNAL OF CLINICAL PHARMACY AND THERAPEUTICS, v.36, no.4, pp.496 - 503
Abstract
What is known and Objective: Although Wen-pitang-Hab-Wu-ling-san (WHW), an oriental herbal medicine, has been prescribed for the treatment of chronic renal failure (CRF) in Korean clinics, no studies regarding WHW-drug interactions had been reported. The purpose of this study was to evaluate the possibility that WHW inhibits the catalytic activities of major cytochrome P450 (CYP) isoforms. Methods: The abilities of various WHW extracts to inhibit phenacetin O-de-ethylation (CYP1A2), tolbutamide 4-methylhydroxylation (CYP2C9), omeprazole 4'-hydroxylation (CYP2C19), dextromethorphan O-demethylation (CYP2D6), chlorzoxazone 6-hydroxylation (CYP2E1) and midazolam 1-hydroxylation (CYP3A4) were assessed using human liver microsomes. Results and Discussion: WHW extract at concentrations up to 100 mu M showed negligible inhibition of the six CYP isoforms tested (CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP2E1 and CYP3A4), with apparent IC(50) values (concentration of the inhibitor causing 50% inhibition of the original enzyme activity) of 817.5, 601.6, 521.7, 310.2, 342.8 and 487.0 mu g/mL, respectively. What is new and Conclusion: Our in vitro findings suggest that WHW extract at concentrations corresponding to a clinically recommended dosage range has no notable inhibitory effects on CYP isoforms. Therefore, we believe that WHW extract may be free of drug-herb interactions when co-administered with other medicines. However, in vivo human studies are needed to confirm these results.
URI
http://hdl.handle.net/YU.REPOSITORY/24745http://dx.doi.org/10.1111/j.1365-2710.2010.01201.x
ISSN
0269-4727
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약학대학 > 약학부 > Articles
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