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Effect of OATP1B1 (SLCO1B1) variant alleles on the pharmacokinetics of pitavastatin in healthy volunteers

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dc.contributor.authorChung, Jae-Yong-
dc.contributor.authorCho, Joo-Youn-
dc.contributor.authorYu, Kyung-Sang-
dc.contributor.authorKim, Jung-Ryul-
dc.contributor.authorOh, Dal-Seok-
dc.contributor.authorJung, Hye-Ryung-
dc.contributor.authorLim, Kyoung-Soo-
dc.contributor.authorMoon, Ki-Ho-
dc.contributor.authorShin, Sang-Goo-
dc.contributor.authorJang, In-Jin-
dc.date.accessioned2009-12-31T05:13:30Z-
dc.date.available2009-12-31T05:13:30Z-
dc.date.issued2005-10-04-
dc.identifier.citationClin Pharmacol Ther. 2005 Oct;78(4):342-50.en
dc.identifier.issn0009-9236 (Print)-
dc.identifier.urihttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16198653-
dc.identifier.urihttp://hdl.handle.net/10371/24410-
dc.description.abstractBACKGROUND: Pitavastatin is a potent, newly developed 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor for the treatment of hyperlipidemia. We characterized the effects of organic anion transporting polypeptide 1 B 1 (OATP 1 B 1) alleles *1a, *1b, and *15 on the pharmacokinetics of pitavastatin. METHODS: Twenty-four healthy Korean volunteers who had previously participated in a pharmacokinetic study of pitavastatin (single oral dose, 1--8 mg) were further investigated. Subjects were grouped according to OATP 1 B 1 genotype. Dose-normalized area under the plasma concentration-time curve (AUC) and peak plasma concentration (C(max)) values were analyzed, because different dosages were administered to subjects, whereas the pharmacokinetics showed linear characteristics. RESULTS: Dose-normalized pitavastatin AUCs for *1b/*1b (group 1), *1a/*1a or *1a/*1b (group 2), and *1a/*15 or *1b/*15 (group 3) were 38.8+/-13.3, 54.4 +/-12.4, and 68.1+/-6.3 ng.h.mL(-1).mg(-1) (mean+/-SD), respectively, with significant differences between all 3 groups (P=.008) and between subjects carrying and those not carrying the *15 allele (P = .004). Dose-normalized pitavastatin C(max) values were 13.2+/- 3.3, 18.2+/-5.7, and 29.4+/- 9.6 ng.mL(-1).mg(-1) in groups 1, 2, and 3, respectively, and also showed significant differences (P=.003) in a manner similar to that shown by AUC. No significant differences were found between the genotype groups in terms of dose-normalized AUC or C(max) values of pitavastatin lactone. CONCLUSION: OATP 1 B 1 variant haplotypes were found to have a significant effect on the pharmacokinetics of pitavastatin. These results suggest that the *15 allele is associated with decreased pitavastatin uptake from blood into hepatocytes and that OATP 1 B 1 genetic polymorphisms have no effect on the pharmacokinetics of pitavastatin lactone.en
dc.language.isoenen
dc.publisherElsevieren
dc.subjectAdulten
dc.subjectAllelesen
dc.subjectArea Under Curveen
dc.subjectAsian Continental Ancestry Groupen
dc.subjectDose-Response Relationship, Drugen
dc.subjectGenotypeen
dc.subjectHalf-Lifeen
dc.subjectHumansen
dc.subjectHydroxymethylglutaryl-CoA Reductase Inhibitors/blood/*pharmacokineticsen
dc.subjectKoreaen
dc.subjectMaleen
dc.subjectOrganic Anion Transporters/*geneticsen
dc.subjectQuinolines/blood/*pharmacokineticsen
dc.titleEffect of OATP1B1 (SLCO1B1) variant alleles on the pharmacokinetics of pitavastatin in healthy volunteersen
dc.typeArticleen
dc.contributor.AlternativeAuthor정재용-
dc.contributor.AlternativeAuthor조주연-
dc.contributor.AlternativeAuthor유경상-
dc.contributor.AlternativeAuthor김정렬-
dc.contributor.AlternativeAuthor오달석-
dc.contributor.AlternativeAuthor정혜령-
dc.contributor.AlternativeAuthor임경수-
dc.contributor.AlternativeAuthor문기호-
dc.contributor.AlternativeAuthor신상구-
dc.contributor.AlternativeAuthor장인진-
dc.identifier.doi10.1016/j.clpt.2005.07.003-
Appears in Collections:
College of Medicine/School of Medicine (의과대학/대학원)Pharmacology (약리학전공)Journal Papers (저널논문_약리학전공)
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