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Int. J. Mol. Sci. 2013, 14(7), 14064-14075;

Effects of Ospemifene on Drug Metabolism Mediated by Cytochrome P450 Enzymes in Humans in Vitro and in Vivo

Department of Pharmacology and Toxicology, University of Oulu, Oulu 90230, Finland
Technopolis Plc, Oulu 90590, Finland
Clinical Research Services Turku, Institute of Biomedicine, Turku 20520, Finland
Pharma Ltd., Turku 20520, Finland
Vitabalans Ltd., Hämeenlinna 13500, Finland
Hormos Medical Ltd., Turku 20520, Finland
Author to whom correspondence should be addressed.
Received: 14 June 2013 / Revised: 27 June 2013 / Accepted: 28 June 2013 / Published: 5 July 2013
(This article belongs to the Special Issue Xenobiotic Metabolism)
Full-Text   |   PDF [664 KB, uploaded 19 June 2014]


The objective of these investigations was to determine the possible effects of the novel selective estrogen receptor modulator, ospemifene, on cytochrome P450 (CYP)-mediated drug metabolism. Ospemifene underwent testing for possible effects on CYP enzyme activity in human liver microsomes and in isolated human hepatocytes. Based on the results obtained in vitro, three Phase 1 crossover pharmacokinetic studies were conducted in healthy postmenopausal women to assess the in vivo effects of ospemifene on CYP-mediated drug metabolism. Ospemifene and its main metabolites 4-hydroxyospemifene and 4'-hydroxyospemifene weakly inhibited a number of CYPs (CYP2B6, CYP2C9, CYP2C19, CYP2C8, and CYP2D6) in vitro. However, only CYP2C9 activity was inhibited by 4-hydroxyospemifene at clinically relevant concentrations. Induction of CYPs by ospemifene in cultured human hepatocytes was 2.4-fold or less. The in vivo studies showed that ospemifene did not have significant effects on the areas under the plasma concentration-time curves of the tested CYP substrates warfarin (CYP2C9), bupropion (CYP2B6) and omeprazole (CYP2C19), demonstrating that pretreatment with ospemifene did not alter their metabolism. Therefore, the risk that ospemifene will affect the pharmacokinetics of drugs that are substrates for CYP enzymes is low. View Full-Text
Keywords: bupropion; CYP; omeprazole; selective estrogen receptor modulator; warfarin bupropion; CYP; omeprazole; selective estrogen receptor modulator; warfarin
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

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Turpeinen, M.; Uusitalo, J.; Lehtinen, T.; Kailajärvi, M.; Pelkonen, O.; Vuorinen, J.; Tapanainen, P.; Stjernschantz, C.; Lammintausta, R.; Scheinin, M. Effects of Ospemifene on Drug Metabolism Mediated by Cytochrome P450 Enzymes in Humans in Vitro and in Vivo. Int. J. Mol. Sci. 2013, 14, 14064-14075.

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