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The effect of the newly developed angiotensin receptor II antagonist fimasartan on the pharmacokinetics of atorvastatin in relation to OATP1B1 in healthy male volunteers

DC Field Value Language
dc.contributor.author이민구-
dc.date.accessioned2014-12-20T17:47:17Z-
dc.date.available2014-12-20T17:47:17Z-
dc.date.issued2011-
dc.identifier.issn0160-2446-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/95251-
dc.description.abstractOBJECTIVE: Interactions between coadministered drugs may unfavorably affect pharmacokinetics. This study evaluated whether fimasartan, an angiotensin receptor II antagonist, affected the pharmacokinetics of atorvastatin. METHODS: A randomized, open-label, 2-period, 2-sequence, crossover, multiple-dosing study was conducted with 24 healthy male volunteers. Twelve subjects received 80-mg atorvastatin once daily for 7 days; later, they received 80-mg atorvastatin with 240-mg fimasartan for 7 days. Twelve other subjects received the same drugs in the opposite sequence. Blood samples were collected scheduled intervals for 24 hours after the last dosing to determine plasma concentrations of atorvastatin acid, atorvastatin lactone, 2-hydroxy atorvastatin acid, and 2-hydroxy atorvastatin lactone. RESULTS: Compared with atorvastatin alone, coadministration of fimasartan and atorvastatin increased the atorvastatin acid mean (95% confidence interval) maximum concentration (Cmax,ss) by 1.89-fold (1.49-2.39) and the area under the concentration curve (AUCτ,ss) by 1.19-fold (0.96-1.48). Fimasartan also increased the mean 2-hydroxy atorvastatin acid Cmax,ss and AUCτ,ss by 2.45-fold (1.80-3.35) and 1.42-fold (1.09-1.85), respectively. The Cmax,ss and AUCτ,ss of the lactone forms of atorvastatin showed smaller changes than those observed for the acidic forms. CONCLUSION: We showed that fimasartan raised plasma atorvastatin concentrations. In vitro tests suggested that this effect may have been mediated by fimasartan inhibition of organic anion-transporting polypeptide 1B1.-
dc.description.statementOfResponsibilityopen-
dc.format.extent492~499-
dc.relation.isPartOfJOURNAL OF CARDIOVASCULAR PHARMACOLOGY-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/2.0/kr/-
dc.subject.MESHAdult-
dc.subject.MESHAngiotensin II Type 1 Receptor Blockers/pharmacology*-
dc.subject.MESHArea Under Curve-
dc.subject.MESHAtorvastatin Calcium-
dc.subject.MESHBiphenyl Compounds/pharmacology*-
dc.subject.MESHCross-Over Studies-
dc.subject.MESHDrug Interactions/physiology-
dc.subject.MESHEstrone/analogs & derivatives-
dc.subject.MESHEstrone/metabolism-
dc.subject.MESHHeptanoic Acids/adverse effects-
dc.subject.MESHHeptanoic Acids/blood-
dc.subject.MESHHeptanoic Acids/metabolism-
dc.subject.MESHHeptanoic Acids/pharmacokinetics*-
dc.subject.MESHHumans-
dc.subject.MESHHydroxymethylglutaryl-CoA Reductase Inhibitors/blood-
dc.subject.MESHHydroxymethylglutaryl-CoA Reductase Inhibitors/metabolism-
dc.subject.MESHHydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacokinetics-
dc.subject.MESHMale-
dc.subject.MESHOrganic Anion Transporters/drug effects*-
dc.subject.MESHOrganic Anion Transporters/genetics-
dc.subject.MESHOrganic Anion Transporters/metabolism-
dc.subject.MESHPyrimidines/pharmacology*-
dc.subject.MESHPyrroles/adverse effects-
dc.subject.MESHPyrroles/blood-
dc.subject.MESHPyrroles/metabolism-
dc.subject.MESHPyrroles/pharmacokinetics*-
dc.subject.MESHRNA, Complementary/genetics-
dc.subject.MESHSolute Carrier Organic Anion Transporter Family Member 1b1-
dc.subject.MESHTetrazoles/pharmacology*-
dc.subject.MESHYoung Adult-
dc.titleThe effect of the newly developed angiotensin receptor II antagonist fimasartan on the pharmacokinetics of atorvastatin in relation to OATP1B1 in healthy male volunteers-
dc.typeArticle-
dc.contributor.collegeCollege of Medicine (의과대학)-
dc.contributor.departmentDept. of Pharmacology (약리학)-
dc.contributor.googleauthorShin, Kwang-Hee-
dc.contributor.googleauthorKim, Tae-Eun-
dc.contributor.googleauthorKim, Sung Eun-
dc.contributor.googleauthorLee, Min Goo-
dc.contributor.googleauthorSong, Im-Sook-
dc.contributor.googleauthorYoon, Seo Hyun-
dc.contributor.googleauthorCho, Joo-Youn-
dc.contributor.googleauthorJang, In-Jin-
dc.contributor.googleauthorShin, Sang-Goo-
dc.contributor.googleauthorYu, Kyung-Sang-
dc.identifier.doi10.1097/FJC.0b013e31822b9092-
dc.admin.authorfalse-
dc.admin.mappingfalse-
dc.contributor.localIdA02781-
dc.relation.journalcodeJ01296-
dc.identifier.eissn1533-4023-
dc.identifier.pmid21765368-
dc.identifier.urlhttp://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&AN=00005344-201111000-00007&LSLINK=80&D=ovft-
dc.subject.keywordfimasartan-
dc.subject.keywordatorvastatin-
dc.subject.keywordpharmacokinetics-
dc.subject.keyworddrug interaction-
dc.subject.keywordOATP1B1-
dc.contributor.alternativeNameLee, Min Goo-
dc.contributor.affiliatedAuthorLee, Min Goo-
dc.rights.accessRightsnot free-
dc.citation.volume58-
dc.citation.number5-
dc.citation.startPage492-
dc.citation.endPage499-
dc.identifier.bibliographicCitationJOURNAL OF CARDIOVASCULAR PHARMACOLOGY, Vol.58(5) : 492-499, 2011-
dc.identifier.rimsid28207-
dc.type.rimsART-
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Pharmacology (약리학교실) > 1. Journal Papers

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