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Effects of Ginkgo biloba extracts on diazepam metabolism: a pharmacokinetic study in healthy Chinese male subjects

  • Pharmacokinetics and Disposition
  • Published:
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Abstract

Aim

It has been reported that Ginkgo biloba extract (GBE) is an inducer or inhibitor of microsomal cytochrome P450 (CYP) 2C19, and diazepam is a substrate of CYP2C19. Thus, it could be expected that GBE may alter the metabolism of diazepam.

Methods

The pharmacokinetic parameters of diazepam and one of its metabolites, N-demethyldiazepam, were compared after oral administration of diazepam (10 mg) in the absence or presence of oral GBE (120 mg bid, for 28 days) in 12 healthy volunteers. The pharmacokinetic analysis was performed using a noncompartmental method.

Results

The 90% confidence intervals (CIs) of the ratios of mean pharmacokinetic parameters of diazepam presence and absence of GBE were well within the 80–125% bioequivalence range, indicating no pharmacokinetic interaction. The ratio of AUC0–408 with GBE to AUC0–408 without GBE was 95.2 (90%CI: 91.6–98.8) and 101.8 (90%CI: 99.4–104.1) for diazepam and N-desmethyldiazepam, respectively. The two drugs were well tolerated, and no drug-related serious adverse events were reported.

Conclusion

The above data suggest that GBE, when taken in normally recommended doses over a 4-week time period, may not affect the pharmacokinetics of diazepam via CYP2C19 and the excretion of N-desmethyldiazepam in healthy volunteers. No drug-drug interaction was observed between GBE and diazepam.

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Acknowledgments

We are grateful to Yangzijiang Pharmaceutical (China) for supplying the GBE tablets, and Professor Yurong Zhang of the Institute of Criminal Science and Technology in Shanghai Public Security Bureau for N-desmethyldiazepam provision and for facilitating the whole project. This work was supported by China Hunan Provincial Health Department Project (no. B2006-083).

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Authors and Affiliations

  1. Clinical Pharmacy and Pharmacology Research Institute, Third Xiangya Hospital, Central South University, Changsha, 410013, China

    Xiao-Cong Zuo, Bi-Kui Zhang, Su-Jie Jia & Shi-Kun Liu

  2. School of Pharmaceutical Sciences, Central South University, Changsha, 410013, China

    Ling-Yun Zhou, Jing Li, Jie Zhang & Ling-Ling Dai

  3. Bioanalytical Chemistry Research Laboratory, Modern Analytical Test Center of Central South University, Changsha, 410009, China

    Ben-Mei Chen

  4. Medical Laboratory Centre, Third Xiangya Hospital, Central South University, Changsha, 410013, China

    Guo-Ping Yang

  5. Medical Laboratory Centre, Third Xiangya Hospital, Central South University, Changsha, 410013, China

    Hong Yuan

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  1. Xiao-Cong Zuo
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Correspondence to Hong Yuan.

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Zuo, XC., Zhang, BK., Jia, SJ. et al. Effects of Ginkgo biloba extracts on diazepam metabolism: a pharmacokinetic study in healthy Chinese male subjects. Eur J Clin Pharmacol 66, 503–509 (2010). https://doi.org/10.1007/s00228-010-0795-4

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  • DOI: https://doi.org/10.1007/s00228-010-0795-4

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