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Open AccessArticle

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

1
Department of Pharmacology and Toxicology, University of Oulu, Oulu 90230, Finland
2
Technopolis Plc, Oulu 90590, Finland
3
Clinical Research Services Turku, Institute of Biomedicine, Turku 20520, Finland
4
Pharma Ltd., Turku 20520, Finland
5
Vitabalans Ltd., Hämeenlinna 13500, Finland
6
Hormos Medical Ltd., Turku 20520, Finland
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2013, 14(7), 14064-14075; https://doi.org/10.3390/ijms140714064
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)
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
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MDPI and ACS Style

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. https://doi.org/10.3390/ijms140714064

AMA Style

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. International Journal of Molecular Sciences. 2013; 14(7):14064-14075. https://doi.org/10.3390/ijms140714064

Chicago/Turabian Style

Turpeinen, Miia; Uusitalo, Jouko; Lehtinen, Terhi; Kailajärvi, Marita; Pelkonen, Olavi; Vuorinen, Jouni; Tapanainen, Pasi; Stjernschantz, Camilla; Lammintausta, Risto; Scheinin, Mika. 2013. "Effects of Ospemifene on Drug Metabolism Mediated by Cytochrome P450 Enzymes in Humans in Vitro and in Vivo" Int. J. Mol. Sci. 14, no. 7: 14064-14075. https://doi.org/10.3390/ijms140714064

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