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Pharmacokinetic comparison of controlled-release and immediate-release oral formulations of simvastatin in healthy Korean subjects: a randomized, open-label, parallel-group, single- and multiple-dose study

DC FieldValueLanguage
dc.contributor.author김경환-
dc.contributor.author박경수-
dc.contributor.author박민수-
dc.contributor.author이윤정-
dc.contributor.author임아영-
dc.contributor.author장성복-
dc.date.accessioned2015-04-23T16:26:32Z-
dc.date.available2015-04-23T16:26:32Z-
dc.date.issued2010-
dc.identifier.issn0149-2918-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/100589-
dc.description.abstractBACKGROUND: A controlled-release (CR) formulation of simvastatin was recently developed in Korea. The formulation is expected to yield a lower C(max) and similar AUC values compared with the immediate-release (IR) formulation. OBJECTIVE: The goal of this study was to compare the pharmacokinetics of the new CR formulation and an IR formulation of simvastatin after single- and multiple-dose administration in healthy Korean subjects. This study was developed as part of a product development project at the request of the Korean regulatory agency. METHODS: This was a randomized, open-label, parallelgroup, 2-part study. Eligible subjects were healthy male or female volunteers between the ages of 19 and 55 years and within 20% of their ideal weight. In part I, each subject received a single dose of the CR or IR formulation of simvastatin 40 mg orally (20 mg x 2 tablets) after fasting. In part II, each subject received the same dose of the CR or IR formulation for 8 consecutive days. Blood samples were obtained for 48 hours after the dose in part I and after the first and the last dose in part II. Pharmacokinetic parameters were determined for both simvastatin (the inactive prodrug) and simvastatin acid (the active moiety). An adverse event (AE) was defined as any unfavorable sign (including an abnormal laboratory finding) or symptom, regardless of whether it had a causal relationship with the study medication. Serious AEs were defined as any events that are considered life threatening, require hospitalization or prolongation of existing hospitalization, cause persistent or significant disability or incapacity, or result in congenital abnormality, birth defect, or death. AEs were determined based on patient interviews and physical examinations. RESULTS: Twenty-four healthy subjects (17 men, 7 women; mean [SD] age, 29 [7] years; age range, 22-50 years) were enrolled in part I, and 29 subjects (17 men, 12 women; mean age, 33 [9] years; age range, 19-55 years) were enrolled in part II. For simvastatin acid, C(max) was significantly smaller (1.68 vs 3.62 ng/mL; P < 0.013) and T(max) and apparent t((1/2)) significantly longer (10.33 vs 4.04 hours [P < 0.001] and 11.41 vs 4.16 hours [P < 0.011]) for the CR formulation compared with the IR formulation, respectively, after the single-dose administration. After the multiple-dose administration, for simvastatin acid, the C(max) for the CR formulation was significantly smaller (3.40 vs 5.16 ng/mL; P < 0.037), while the values for T(max) and apparent t((1/2)) were significantly longer (8.40 vs 4.57 hours and 13.09 vs 4.52 hours; both, P < 0.001) compared with the IR formulation. There was no significant difference between the CR and the IR formulations for AUC(0-last) and AUC(0-infinity)) during either the single- or multiple-dose testing. Both CR and IR formulations were well tolerated in all subjects, and no serious AEs or adverse drug reactions were found. No subjects reported any AEs during part I of the study. During part II, 6 subjects (3 from each formulation group) reported headache, 1 reported lumbago before the dose, and 1 subject had a hordeolum while receiving the CR formulation. CONCLUSIONS: The C(max) of the simvastatin CR formulation was found to be significantly smaller while the AUC of the active moiety did not differ significantly from that of the IR formulation in these healthy Korean subjects. The simvastatin CR and IR formulations were well tolerated, with no serious AEs observed. To evaluate the characteristics of the CR formulation, its clinical efficacy must be examined in patient populations-
dc.description.statementOfResponsibilityopen-
dc.format.extent206~216-
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.MESHAdministration, Oral-
dc.subject.MESHAdult-
dc.subject.MESHArea Under Curve-
dc.subject.MESHAsian Continental Ancestry Group-
dc.subject.MESHCalcium Channel Blockers/administration & dosage-
dc.subject.MESHCalcium Channel Blockers/pharmacokinetics*-
dc.subject.MESHChromatography, High Pressure Liquid-
dc.subject.MESHDelayed-Action Preparations-
dc.subject.MESHDose-Response Relationship, Drug-
dc.subject.MESHElectrocardiography-
dc.subject.MESHFemale-
dc.subject.MESHHumans-
dc.subject.MESHKorea-
dc.subject.MESHMale-
dc.subject.MESHMiddle Aged-
dc.subject.MESHReference Values-
dc.subject.MESHSimvastatin/administration & dosage-
dc.subject.MESHSimvastatin/pharmacokinetics*-
dc.subject.MESHTandem Mass Spectrometry-
dc.subject.MESHYoung Adult-
dc.titlePharmacokinetic comparison of controlled-release and immediate-release oral formulations of simvastatin in healthy Korean subjects: a randomized, open-label, parallel-group, single- and multiple-dose study-
dc.typeArticle-
dc.contributor.collegeCollege of Medicine (의과대학)-
dc.contributor.departmentDept. of Pediatrics (소아과학)-
dc.contributor.googleauthorJae Yong Chung-
dc.contributor.googleauthorYoon Jung Lee-
dc.contributor.googleauthorSeong Bok Jang-
dc.contributor.googleauthorLay Ahyoung Lim-
dc.contributor.googleauthorMin Soo Park-
dc.contributor.googleauthorKyung Hwan Kim-
dc.identifier.doi10.1016/j.clinthera.2010.01.026-
dc.admin.authorfalse-
dc.admin.mappingfalse-
dc.contributor.localIdA00311-
dc.contributor.localIdA01422-
dc.contributor.localIdA01468-
dc.contributor.localIdA03023-
dc.contributor.localIdA03383-
dc.contributor.localIdA03436-
dc.relation.journalcodeJ00614-
dc.identifier.eissn1879-114X-
dc.identifier.pmid20171425-
dc.identifier.urlhttp://www.sciencedirect.com/science/article/pii/S0149291810000275-
dc.subject.keywordsimvastatin-
dc.subject.keywordsimvastatin acid-
dc.subject.keywordpharmacokinetics-
dc.subject.keywordcontrolled-release formulation-
dc.contributor.alternativeNameKim, Kyung Hwan-
dc.contributor.alternativeNamePark, Kyung Soo-
dc.contributor.alternativeNamePark, Min Soo-
dc.contributor.alternativeNameLee, Yoon Jung-
dc.contributor.alternativeNameLim, Lay Ahyoung-
dc.contributor.alternativeNameJang, Seong Bok-
dc.contributor.affiliatedAuthorKim, Kyung Hwan-
dc.contributor.affiliatedAuthorPark, Kyung Soo-
dc.contributor.affiliatedAuthorPark, Min Soo-
dc.contributor.affiliatedAuthorLee, Yoon Jung-
dc.contributor.affiliatedAuthorLim, Lay Ahyoung-
dc.contributor.affiliatedAuthorJang, Seong Bok-
dc.citation.volume32-
dc.citation.number1-
dc.citation.startPage206-
dc.citation.endPage216-
dc.identifier.bibliographicCitationCLINICAL THERAPEUTICS, Vol.32(1) : 206-216, 2010-
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Pediatrics (소아청소년과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pharmacology (약리학교실) > 1. Journal Papers

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