PMID: 11902809Mar 21, 2002Paper

Simvastatin and lovastatin, but not pravastatin, interact with MDR1

The Journal of Pharmacy and Pharmacology
Toshiyuki SakaedaKatsuhiko Okumura

Abstract

The 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, pravastatin, was compared with simvastatin and lovastatin from the viewpoint of susceptibility to interaction with or via the multidrug transporter, MDR1 (P-glycoprotein). This was carried out using the MDR1-overexpressing cell line LLC-GA5-COL150, established by transfection of MDR1 cDNA into porcine kidney epithelial LLC-PK1 cells, and [3H]digoxin, which is a well-documented substrate for MDR1. Pravastatin, at 25-100 microM, had no effect on the transcellular transport of [3H]digoxin whereas simvastatin and lovastatin suppressed the basal-to-apical transport of [3H]digoxin and increased the apical-to-basal transport. It was suggested that recognition by MDR1 was due to the hydrophobicity. In conclusion, simvastatin and lovastatin are susceptible to interaction with or via MDR1, but pravastatin is not. This is important information when selecting the HMG-CoA reductase inhibitors for patients taking drugs that are MDR1 substrates.

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Citations

Jun 26, 2003·Journal of Biomedical Science·Kuo-Chin HuangWan-Wan Lin
Apr 9, 2013·Naunyn-Schmiedeberg's Archives of Pharmacology·Martin WernerMartin Hohenegger
Oct 14, 2009·European Journal of Clinical Pharmacology·Ryuji KatoKazuhiko Tanaka
Oct 25, 2006·Pharmaceutical Research·Wei C Lau, Paul A Gurbel
Nov 1, 2002·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·C Bradley HareHarry W Lampiris
Nov 25, 2003·Gut·C G DietrichR P J Oude Elferink
Nov 7, 2002·Biological & Pharmaceutical Bulletin·Toshiyuki SakaedaKatsuhiko Okumura
Sep 3, 2013·Biological & Pharmaceutical Bulletin·Takuro KoboriShogo Tokuyama
Jul 2, 2003·Pharmacogenomics·Toshiyuki SakaedaKatsuhiko Okumura
Jun 18, 2004·Drugs·Alberto CorsiniChristie M Ballantyne
Mar 18, 2004·British Journal of Clinical Pharmacology·Ichiro FukazawaHajime Yasuhara
Mar 3, 2007·The Journal of Pharmacy and Pharmacology·Koichi IwakiKatsuhiko Okumura
Oct 27, 2006·Pharmacotherapy·Carol W HoltzmanSarah A Spinler
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Jan 18, 2006·Drug Metabolism and Pharmacokinetics·Toshiyuki Sakaeda
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