Effects of four traditional Chinese medicines on the pharmacokinetics of simvastatin

Abstract

1. Concomitant traditional Chinese medicines (TCMs) could be the reason for relative poor efficacy of statins in dyslipidemia patients in China.

2. An open-label, randomized, 5-period crossover study in healthy Chinese was designed to evaluate the pharmacokinetic interaction and tolerability of multiple doses of certain TCMs on a single dose of simvastatin. In each period, subjects received one of five treatments. In Treatment A, subjects received a single dose of 20 mg simvastatin. In Treatment B, C, D or E, subjects received Tong Xin Luo, Nao Xin Tong, Guan Mai Ning or Yin Xing Ye for 7 days and a single dose of 20 mg simvastatin on Day 7. The washout period was 7 days.

3. The 97.5% confidence interval of the AUC_0–48 h geometric mean ratio of simvastatin acid and simvastatin for simvastatin given after multiple oral doses of one of the TCMs versus simvastatin given alone were fully contained within the prespecified bounds of (0.50, 2.00).

4. Exposures to simvastatin acid and simvastatin following a single dose of simvastatin alone were similar to those following coadministration of a single dose of simvastatin with multiple doses of each of the TCM preparations tested. Simvastatin and these TCMs were well tolerated.

• Drug–drug interaction
• Guan Mai Ning
• Nao Xin Tong
• pharmacokinetics
• simvastatin
• simvastatin hydroxyacid
• Tong Xin Luo
• Yin Xing Ye

Acknowledgements

The authors would like to thank staff in the study team and all study subjects.

Declaration of interest

The authors declare no conflict of interest. This study was sponsored by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc. The work was also supported by a grant from the National Program on Key Research Project of New Drug Innovation (No. 2012ZX09303006-002).