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Effect of Ketoconazole on Lobeglitazone Pharmacokinetics in Korean Volunteers

DC FieldValueLanguage
dc.contributor.author김윤남-
dc.contributor.author박민수-
dc.contributor.author김춘옥-
dc.date.accessioned2015-01-06T17:17:28Z-
dc.date.available2015-01-06T17:17:28Z-
dc.date.issued2014-
dc.identifier.issn0149-2918-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/99700-
dc.description.abstractPURPOSE: Lobeglitazone, a peroxisome proliferator-activated receptor-γ agonist, is metabolized primarily by the cytochrome P450 (CYP) 3A4 isoenzyme. Individuals concomitantly taking lobeglitazone and a CYP3A4 inhibitor may experience some adverse effects secondary to increased systemic exposure to lobeglitazone. To address such potential concern, we evaluated the effects of ketoconazole, a prototypic CYP3A4 inhibitor, on the pharmacokinetic (PK) properties and associated adverse effects of lobeglitazone. METHODS: A PK drug-drug interaction study was conducted in healthy individuals between 20 and 45 years old in a randomized, open-label, 2-way crossover design. Even though the PK study was performed on a single dose of lobeglitazone, multiple ketoconazole doses were given to ensure that the full extent of inhibition of CYP3A4 was maintained during the PK sampling. All study participants received a single oral dose of lobeglitazone 0.5 mg with or without 9 oral 200-mg doses of ketoconazole pretreatment twice daily. The primary PK parameter end points (AUC and Cmax) were estimated using noncompartmental analysis, and the 90% CIs for the geometric mean ratios (ratio of lobeglitazone and ketoconazole to lobeglitazone alone) were investigated. Tolerability (adverse events, vital signs, ECG, and laboratory tests) was also assessed. FINDINGS: A total of 24 Korean men (mean age, 26 years; age range, 20-32 years; mean weight, 68 kg; weight range, 59-81 kg) completed the study and were evaluable for lobeglitazone PK properties and tolerability. The mean (SD) Cmax values of lobeglitazone with and without ketoconazole were 49 (7) ng/mL and 48 (6) ng/mL at 1.5 and 1.0 hours after dosing, respectively. The mean (SD) AUC∞ values were 532 (117) ng·h/mL and 405 (110) ng·h/mL, respectively. Although the Cmax was not significantly affected, the geometric mean ratio for AUC∞ was increased by a point estimate of 1.33 (90% CI, 1.23-1.44). A single oral administration of lobeglitazone 0.5 mg with or without ketoconazole pretreatment did not produce any clinically significant adverse effects on vital signs, 12-lead ECG profiles, or laboratory tests. IMPLICATIONS: The administration of lobeglitazone, 0.5 mg alone or in combination with multiple doses of ketoconazole, was generally well tolerated. The systemic exposure of lobeglitazone was increased to a modest extent by pretreatment with 9 twice-daily doses of ketoconazole. Clinicaltrials.gov identifier: NCT01330563.-
dc.description.statementOfResponsibilityopen-
dc.format.extent1064~1071-
dc.relation.isPartOfCLINICAL THERAPEUTICS-
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.MESHCross-Over Studies-
dc.subject.MESHDrug Interactions-
dc.subject.MESHHealthy Volunteers-
dc.subject.MESHHumans-
dc.subject.MESHKetoconazole/administration & dosage*-
dc.subject.MESHMale-
dc.subject.MESHMiddle Aged-
dc.subject.MESHPyrimidines/administration & dosage-
dc.subject.MESHPyrimidines/adverse effects*-
dc.subject.MESHPyrimidines/pharmacokinetics*-
dc.subject.MESHRepublic of Korea-
dc.subject.MESHThiazolidinediones/administration & dosage-
dc.subject.MESHThiazolidinediones/adverse effects*-
dc.subject.MESHThiazolidinediones/pharmacokinetics*-
dc.subject.MESHYoung Adult-
dc.titleEffect of Ketoconazole on Lobeglitazone Pharmacokinetics in Korean Volunteers-
dc.typeArticle-
dc.contributor.collegeCollege of Medicine (의과대학)-
dc.contributor.departmentDept. of Biostatistics (의학통계학)-
dc.contributor.googleauthorEun Sil Oh-
dc.contributor.googleauthorChoon Ok Kim-
dc.contributor.googleauthorKi Hyon Kim-
dc.contributor.googleauthorYoun Nam Kim-
dc.contributor.googleauthorChin Kim-
dc.contributor.googleauthorJangik I. Lee-
dc.contributor.googleauthorMin Soo Park-
dc.identifier.doi10.1016/j.clinthera.2014.05.064-
dc.admin.authorfalse-
dc.admin.mappingfalse-
dc.contributor.localIdA01468-
dc.contributor.localIdA04535-
dc.contributor.localIdT999900113-
dc.contributor.localIdA04735-
dc.relation.journalcodeJ00614-
dc.identifier.eissn1879-114X-
dc.identifier.pmid25047497-
dc.identifier.urlhttp://www.sciencedirect.com/science/article/pii/S0149291814003555-
dc.subject.keywordCYP3A4-
dc.subject.keyworddrug interaction ketoconazole-
dc.subject.keywordlobeglitazone-
dc.subject.keywordpharmacokinetics-
dc.contributor.alternativeNameKim, Youn Nam-
dc.contributor.alternativeNamePark, Min Soo-
dc.contributor.affiliatedAuthorPark, Min Soo-
dc.contributor.affiliatedAuthorKim, Youn Nam-
dc.rights.accessRightsfree-
dc.citation.volume36-
dc.citation.number7-
dc.citation.startPage1064-
dc.citation.endPage1071-
dc.identifier.bibliographicCitationCLINICAL THERAPEUTICS, Vol.36(7) : 1064-1071, 2014-
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Biomedical Systems Informatics (의생명시스템정보학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pediatrics (소아청소년과학교실) > 1. Journal Papers

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