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Effect of OATP1B1 (SLCO1B1) variant alleles on the pharmacokinetics of pitavastatin in healthy volunteers
DC Field | Value | Language |
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dc.contributor.author | Chung, Jae-Yong | - |
dc.contributor.author | Cho, Joo-Youn | - |
dc.contributor.author | Yu, Kyung-Sang | - |
dc.contributor.author | Kim, Jung-Ryul | - |
dc.contributor.author | Oh, Dal-Seok | - |
dc.contributor.author | Jung, Hye-Ryung | - |
dc.contributor.author | Lim, Kyoung-Soo | - |
dc.contributor.author | Moon, Ki-Ho | - |
dc.contributor.author | Shin, Sang-Goo | - |
dc.contributor.author | Jang, In-Jin | - |
dc.date.accessioned | 2009-12-31T05:13:30Z | - |
dc.date.available | 2009-12-31T05:13:30Z | - |
dc.date.issued | 2005-10-04 | - |
dc.identifier.citation | Clin Pharmacol Ther. 2005 Oct;78(4):342-50. | en |
dc.identifier.issn | 0009-9236 (Print) | - |
dc.identifier.uri | http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16198653 | - |
dc.identifier.uri | https://hdl.handle.net/10371/24410 | - |
dc.description.abstract | BACKGROUND: 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.iso | en | en |
dc.publisher | Elsevier | en |
dc.subject | Adult | en |
dc.subject | Alleles | en |
dc.subject | Area Under Curve | en |
dc.subject | Asian Continental Ancestry Group | en |
dc.subject | Dose-Response Relationship, Drug | en |
dc.subject | Genotype | en |
dc.subject | Half-Life | en |
dc.subject | Humans | en |
dc.subject | Hydroxymethylglutaryl-CoA Reductase Inhibitors/blood/*pharmacokinetics | en |
dc.subject | Korea | en |
dc.subject | Male | en |
dc.subject | Organic Anion Transporters/*genetics | en |
dc.subject | Quinolines/blood/*pharmacokinetics | en |
dc.title | Effect of OATP1B1 (SLCO1B1) variant alleles on the pharmacokinetics of pitavastatin in healthy volunteers | en |
dc.type | Article | en |
dc.contributor.AlternativeAuthor | 정재용 | - |
dc.contributor.AlternativeAuthor | 조주연 | - |
dc.contributor.AlternativeAuthor | 유경상 | - |
dc.contributor.AlternativeAuthor | 김정렬 | - |
dc.contributor.AlternativeAuthor | 오달석 | - |
dc.contributor.AlternativeAuthor | 정혜령 | - |
dc.contributor.AlternativeAuthor | 임경수 | - |
dc.contributor.AlternativeAuthor | 문기호 | - |
dc.contributor.AlternativeAuthor | 신상구 | - |
dc.contributor.AlternativeAuthor | 장인진 | - |
dc.identifier.doi | 10.1016/j.clpt.2005.07.003 | - |
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