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Effect of a single-dose rifampin on the pharmacokinetics of pitavastatin in healthy volunteers

  • Pharmacokinetics and Disposition
  • Published:
European Journal of Clinical Pharmacology Aims and scope Submit manuscript

Abstract

Purpose

As an inhibitor of HMG-CoA reductase that catalyses the first step of cholesterol synthesis, pitavastatin undergoes little hepatic metabolism; however, it is a substrate of uptake and efflux transporters. Since pitavastatin is potentially co-administered with agents that affect transporter activities, the pharmacokinetics of pitavastatin was investigated on the effects of a single-dose rifampin in healthy volunteers.

Methods

Twelve Chinese healthy male volunteers took 4 mg pitavastatin orally with 150 ml water or with a single dose of 600 mg rifampin on separate occasions and the plasma concentrations of pitavastatin were measured over 48 h by HPLC-MS/MS.

Results

A single dose of rifampin significantly increased the mean area under the plasma concentration-time curve(AUC)(0-48h) and Cmax of pitavastatin by 573.5 %(95%CI, 373.3–773.7 %, p < 0.001) and 819.2 %(95 % CI, 515.4–1123.0 %, p < 0.001) respectively, while significantly decreased the t1/2 and CL/F of pitavastatin by 38.8 % (95 % CI, 18.2–59.4 %, p < 0.001) and 81.4 % (95 % CI, 75.0–87.7 %, p < 0.001) respectively.

Conclusions

Co-administration of pitavastatin with a single dose of rifampin resulted in a significant increase in plasma levels of pitavastatin in Chinese healthy subjects.

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Acknowledgements

Thanks to the grants from China Postdoctoral Science Foundation(2013 M531817), Young Teachers Boost Plans of Chinese Central College (grant #201012200047), Hunan Provincial Natural Science Foundation of China (Key Project, 10JJ2008) and 863 Project(No. 2012AA02A518) for financial support.

Declaration of interest

The authors report no conflicts of interest.

Funding source

This work was supported by research grants from China Postdoctoral Science Foundation(2013 M531817), Young Teachers Boost Plans of Chinese Central College (grant #201012200047), Hunan Provincial Natural Science Foundation of China (Key Project,10JJ2008) and 863 Project(No. 2012AA02A518).

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Authors and Affiliations

  1. Institute of Clinical Pharmacology, Central South University, Xiang-Ya School of medicine, 110 Xiang-Ya road, Changsha, Hunan, 410078, People’s Republic of China

    Yao Chen, Wei Zhang, Wei-hua Huang, Zhi-rong Tan, Yi-cheng Wang & Hong-Hao Zhou

  2. Laboratory of Ethnopharmacology, Institute of Integrated Traditional Chinese and Western Medicine, Xiangya Hospital, Central South University, 87 Xiangya Road, 410008, Changsha, China

    Yao Chen & Xi Huang

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  1. Yao Chen
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  2. Wei Zhang
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  3. Wei-hua Huang
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  6. Xi Huang
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  7. Hong-Hao Zhou
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Correspondence to Hong-Hao Zhou.

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Chen, Y., Zhang, W., Huang, Wh. et al. Effect of a single-dose rifampin on the pharmacokinetics of pitavastatin in healthy volunteers. Eur J Clin Pharmacol 69, 1933–1938 (2013). https://doi.org/10.1007/s00228-013-1554-0

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  • DOI: https://doi.org/10.1007/s00228-013-1554-0

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