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

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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

Content Provider	Springer Nature Link
Author	Hu, Miao Lee, Hon Kit To, Kenneth K. W. Fok, Benny S. P. Wo, Siu Kwan Ho, Chung Shun Wong, Chun Kwok Zuo, Zhong Chan, Thomas Y. K. Chan, Juliana C. N. Tomlinson, Brian
Copyright Year	2016
Abstract	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.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.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.This study demonstrated that telmisartan significantly increased the systemic exposure to rosuvastatin after single and multiple doses.
Starting Page	1471
Ending Page	1478
Page Count	8
File Format	PDF
ISSN	00316970
Journal	European Journal of Clinical Pharmacology
Volume Number	72
Issue Number	12
e-ISSN	14321041
Language	English
Publisher	Springer Berlin Heidelberg
Publisher Date	2016-09-20
Publisher Place	Berlin, Heidelberg
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	ABCG2 Drug interaction Rosuvastatin Telmisartan Pharmacology/Toxicology
Content Type	Text
Resource Type	Article
Subject	Pharmacology Pharmacology (medical)

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