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

Abstract

WHAT IS KNOWN AND OBJECTIVE:

Although Wen-pi-tang-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 μm 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 μg/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.

• Authors: H W Lee, D W Kim, P B Phapale, M-S Lim, J Park, J J Seo, K M Park, Y-K Park, Y-R Yoon
• Journal: Journal of clinical pharmacy and therapeutics (J Clin Pharm Ther) Vol. 36 Issue 4 Pg. 496-503 (Aug 2011) ISSN: 1365-2710 [Electronic] England
• PMID: 21729114 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2010 The Authors. JCPT © 2010 Blackwell Publishing Ltd.

Chemical References

• Cytochrome P-450 Enzyme Inhibitors
• Drugs, Chinese Herbal
• Isoenzymes
• Wen-pi-tang-Hab-Wu-ling-san
• Cytochrome P-450 Enzyme System

Topics

• Cytochrome P-450 Enzyme Inhibitors
• Cytochrome P-450 Enzyme System (metabolism)
• Dose-Response Relationship, Drug
• Drugs, Chinese Herbal (administration & dosage, pharmacology)
• Herb-Drug Interactions
• Humans
• In Vitro Techniques
• Inhibitory Concentration 50
• Isoenzymes
• Microsomes, Liver (drug effects, enzymology)
• Republic of Korea