Effect of a traditional Chinese medicine Liu Wei Di Huang Wan on the activities of CYP2C19, CYP2D6 and CYP3A4 in healthy volunteers

Abstract

1. Liu Wei Di Huang Wan (LDW), a well-known traditional Chinese medicine, is widely used for the treatment of various diseases in China. This study was designed to investigate the potential herb–drug interactions of LDW in healthy volunteers and attempted to ascertain whether the interaction might be affected by genotypes.

2. We assessed the effect of LDW on the activities of CYP2C19, CYP2D6 and CYP3A4 in 12 Chinese healthy subjects in a single-center, controlled, non-blinded, two-way crossover clinical trial. The subject pool consisted of six extensive metabolizers with CYP2C19*1/*1 and six poor metabolizers with CYP2C19*2/*2. Placebo or 4.8 g LDW (12 pills, 0.2 g/pill, twice daily) was given to each participant for 14 continuous days with a wash-out period of 2 weeks after an oral administration of 30 mg omeprazole, 30 mg dextromethorphan hydrobromide and 7.5 mg midazolam. The activities of CYP2C19, CYP2D6 and CYP3A4 were ascertained by their respective plasma or urinary metabolic ratios on day 14 post-treatment.

3. There is no difference in the activities of the three tested enzymes before or after a 14-day administration of LDW. LDW had no effect on the pharmacokinetic parameters of the substrates and their metabolites.

4. A 14-day administration of LDW did not affect the activities of CYP2C19, CYP2D6 and CYP3A4. LDW is unlikely to cause pharmacokinetic interaction when it is combined with other medications predominantly metabolized by these enzymes.

Keywords::

• Liu Wei Di Huang Wan
• CYP2C19
• CYP2D6
• CYP3A4
• drug interaction

Acknowledgments

We thank the Basic Science Research Fund in CSU (No. 2010QZZD010), Huge Project to Boost Chinese Drug Development (No. 2011ZX09302), National Sci-Tech Support Plan of China (SQ2010BAJY1411-08), National Development of Key Novel Drugs for Special Projects of China (2011ZX09302) and Young Teachers Boost Plans of Chinese Central College (grant #201012200047) for financial support. We thank Dr. Shousong Cao of Roswell Park Cancer Institute (Buffalo, New York) and Visiting Professor of Central South University and Ms Zhuoran Duan for proof reading of the manuscript.

Declaration of interest

Financial support was provided by The Basic Science Research Fund in CSU (No. 2010QZZD010), Huge Project to Boost Chinese Drug Development (No. 2011ZX09302), National Sci-Tech Support Plan of China (SQ2010BAJY1411-08), National Development of Key Novel Drugs for Special Projects of China (2011ZX09302) and Young Teachers Boost Plans of Chinese Central College (grant #201012200047).