title: Simvastatin and lovastatin, but not pravastatin, interact with MDR1.
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.
authors.affiliation: Department of Hospital Pharmacy, School of Medicine, Kobe University, Japan. sakaedat@med.kobe-u.ac.jp
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Sakaeda
authors.forename: Kohji
authors.initials: K
authors.lastname: Takara
authors.forename: Mikio
authors.initials: M
authors.lastname: Kakumoto
authors.forename: Nobuko
authors.initials: N
authors.lastname: Ohmoto
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Nakamura
authors.forename: Koichi
authors.initials: K
authors.lastname: Iwaki
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Tanigawara
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Okumura
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000187:drug effects*; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002478:Cells, Cultured; D004077:Digoxin / Q000378:metabolism; D004347:Drug Interactions; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D008148:Lovastatin / Q000494:pharmacology; D017035:Pravastatin / Q000494:pharmacology; D019821:Simvastatin / Q000494:pharmacology; D013552:Swine
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D004077:Digoxin; D008148:Lovastatin; D019821:Simvastatin; D017035:Pravastatin