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Telmisartan increases systemic exposure to rosuvastatin after single and multiple doses, and in vitro studies show telmisartan inhibits ABCG2-mediated transport of rosuvastatin

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

Abstract

Purpose

The ATP-binding cassette transporter G2 (ABCG2) plays an important role in the disposition of rosuvastatin. Telmisartan, a selective angiotension-II type 1 (AT1) receptor blocker, inhibits the transport capacity of ABCG2, which may result in drug interactions. This study investigated the pharmacokinetic interaction between rosuvastatin and telmisartan and the potential mechanism.

Methods

In this two-phase fixed-order design study, healthy subjects received single doses of 10 mg rosuvastatin at baseline and after telmisartan 40 mg daily for 14 days. Patients with hyperlipidaemia who had been taking rosuvastatin 10 mg daily for at least 4 weeks were given telmisartan 40 mg daily for 14 days together with rosuvastatin. Plasma concentrations of rosuvastatin were measured over 24 h before and after telmisartan administration. In vitro experiments using a bidirectional transport assay were performed to investigate the involvement of ABCG2 in the interaction.

Results

Co-administration of telmisartan significantly increased the maximum plasma concentration (C max) and the area under the plasma concentration–time curve (AUC) of rosuvastatin by 71 and 26 %, respectively. The T max values were reduced after administration of telmisartan. There was no significant difference in the interaction of rosuvastatin with telmisartan between healthy volunteers and patients receiving long-term rosuvastatin therapy or among subjects with the different ABCG2 421 C>A genotypes. The in vitro experiment demonstrated that telmisartan inhibited ABCG2-mediated efflux of rosuvastatin.

Conclusion

This study demonstrated that telmisartan significantly increased the systemic exposure to rosuvastatin after single and multiple doses.

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Acknowledgment

We thank the other members of the research team especially Ms. Swen Ip and Ms. Evelyn Chau for their excellent assistance. We also thank the volunteers for their participation in this research.

Author information

Authors and Affiliations

  1. Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China

    Miao Hu, Hon-Kit Lee, Benny S. P. Fok, Thomas Y. K. Chan, Juliana C. N. Chan & Brian Tomlinson

  2. Department of Chemical Pathology, The Chinese University of Hong Kong, Hong Kong SAR, China

    Hon-Kit Lee, Chung-Shun Ho & Chun-Kwok Wong

  3. School of Pharmacy, The Chinese University of Hong Kong, Hong Kong SAR, China

    Kenneth K. W. To, Siu-Kwan Wo & Zhong Zuo

  4. Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong SAR, China

    Brian Tomlinson

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  1. Miao Hu
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Corresponding author

Correspondence to Brian Tomlinson.

Ethics declarations

The study was conducted in compliance with the Declaration of Helsinki. The study protocol and statement of informed consent were approved by the Joint Clinical Research Ethics Committee of The Chinese University of Hong Kong and New Territories East Cluster (CUHK-NTEC), and this trial was registered at the WHO International Clinical Trials Registry Platform (WHO-ICTRP) as ChiCTR-ONC-13,003,006. All the subjects gave written informed consent.

Electronic supplementary material

Supplementary Figure 1

The plasma concentration–time profiles of rosuvastatin before and after telmisartan in the study subjects stratified by the ABCG2 421C>A genotypes (DOC 107 kb)

Supplementary Figure 2

The plasma concentration–time profiles of rosuvastatin before and after telmisartan in the healthy volunteers and in patients receiving long-term rosuvastatin therapy (DOC 116 kb)

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Hu, M., Lee, HK., To, K.K.W. et al. Telmisartan increases systemic exposure to rosuvastatin after single and multiple doses, and in vitro studies show telmisartan inhibits ABCG2-mediated transport of rosuvastatin. Eur J Clin Pharmacol 72, 1471–1478 (2016). https://doi.org/10.1007/s00228-016-2130-1

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  • DOI: https://doi.org/10.1007/s00228-016-2130-1

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