title: SLCO1B1 (OATP1B1, an uptake transporter) and ABCG2 (BCRP, an efflux transporter) variant alleles and pharmacokinetics of pitavastatin in healthy volunteers.
abstract: To investigate the contribution of genetic polymorphisms of SLCO1B1 and ABCG2 to the pharmacokinetics of a dual substrate, pitavastatin, 2 mg of pitavastatin was administered to 38 healthy volunteers and pharmacokinetic parameters were compared among the following groups: 421C/C(*)1b/(*)1b (group 1), 421C/C(*)1b/(*)15 (group 2), 421C/C(*)15/(*)15 and 421C/A(*)15/(*)15 (group 3), 421C/A(*)1b/(*)1b (group 4), 421A/A(*)1b/(*)1b (group 5), and 421C/A(*)1b/(*)15 (group 6). In SLCO1B1, pitavastatin area under plasma concentration-time curve from 0 to 24 h (AUC(0-24)) for groups 1, 2, and 3 was 81.1+/-18.1, 144+/-32, and 250+/-57 ng h/ml, respectively, with significant differences among all three groups. In contrast to SLCO1B1, AUC(0-24) in groups 1, 4, and 5 was 81.1+/-18.1, 96.7+/-35.4, and 78.2+/-8.2 ng h/ml, respectively. Although the SLCO1B1 polymorphism was found to have a significant effect on the pharmacokinetics of pitavastatin, a nonsynonymous ABCG2 variant, 421C>A, did not appear to be associated with the altered pharmacokinetics of pitavastatin.
authors: Department of Clinical Pharmacokinetics, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
authors: I
authors: I
authors: Ieiri
authors: S
authors: S
authors: Suwannakul
authors: K
authors: K
authors: Maeda
authors: H
authors: H
authors: Uchimaru
authors: K
authors: K
authors: Hashimoto
authors: M
authors: M
authors: Kimura
authors: H
authors: H
authors: Fujino
authors: M
authors: M
authors: Hirano
authors: H
authors: H
authors: Kusuhara
authors: S
authors: S
authors: Irie
authors: S
authors: S
authors: Higuchi
authors: Y
authors: Y
authors: Sugiyama
mesh_terms: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000328:Adult; D000818:Animals; D019540:Area Under Curve; D002853:Chromatography, Liquid; D004791:Enzyme Inhibitors / Q000493:pharmacokinetics; D005787:Gene Frequency; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D007408:Intestinal Absorption; D007783:Lactones / Q000493:pharmacokinetics; D027381:Liver-Specific Organic Anion Transporter 1; D008297:Male; D013058:Mass Spectrometry; D051379:Mice; D009363:Neoplasm Proteins / Q000235:genetics*; D027361:Organic Anion Transporters / Q000235:genetics*; D011110:Polymorphism, Genetic; D011804:Quinolines / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D012016:Reference Values
chemical_list: C116614:ABCG2 protein, human; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D004791:Enzyme Inhibitors; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007783:Lactones; D027381:Liver-Specific Organic Anion Transporter 1; D009363:Neoplasm Proteins; D027361:Organic Anion Transporters; D011804:Quinolines; C503999:SLCO1B1 protein, human; C108475:pitavastatin