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Cited 3 times in

Population pharmacokinetic analysis of diurnal and seasonal variations of plasma concentrations of cilostazol in healthy volunteers.

DC FieldValueLanguage
dc.contributor.author박경수-
dc.contributor.author손한길-
dc.date.accessioned2015-12-28T10:56:28Z-
dc.date.available2015-12-28T10:56:28Z-
dc.date.issued2014-
dc.identifier.issn0163-4356-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/138352-
dc.description.abstractBACKGROUND: The background of this study was (1) to examine factors influencing cilostazol pharmacokinetics by developing a population model incorporating diurnal variation and other covariate effects and (2) to assess the feasibility of applying the developed model to determine the optimal dosing times. METHODS: Data obtained from a cilostazol pharmacokinetic study consisting of 2 clinical trials (a single twice-a-day (BID) dosing trial in winter and a multiple BID dosing trial in summer) conducted in healthy Korean subjects were used for model building. A basic model was built, followed by a diurnal variation model, and then a final model was built incorporating covariates, including a seasonal difference. The optimal morning and evening dosing times were determined from simulations. RESULTS: Diurnal variation in cilostazol pharmacokinetics was explained by the morning absorption rate constant being faster than in the evening, yielding values of 0.278 versus 0.234/h in summer, when 24- and 12-hour circadian rhythms were included in the model. The seasonal variation was explained by a 26.9% and a 31.8% decrease in the absorption rate constant and clearance, respectively, in winter compared with summer. Based on twice-a-day (BID) dosing, dosing times of 9 AM and 5 PM in summer and 10 AM and 7 PM in winter were expected to produce the smallest peak-to-peak fluctuations in cilostazol concentration, possibly minimizing unwanted effects of the drug. CONCLUSIONS: This study demonstrated the intraday and interseasonal time-varying nature of cilostazol pharmacokinetics using a population modeling approach and developed a strategy for optimizing dosing times. It is suggested that these methods can be similarly applied to analyses and controls of other drugs that exhibit characteristics of time-varying pharmacokinetics.-
dc.description.statementOfResponsibilityopen-
dc.format.extent771~780-
dc.relation.isPartOfTHERAPEUTIC DRUG MONITORING-
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.MESHCircadian Rhythm/drug effects-
dc.subject.MESHCircadian Rhythm/physiology*-
dc.subject.MESHFemale-
dc.subject.MESHHealthy Volunteers*-
dc.subject.MESHHumans-
dc.subject.MESHMale-
dc.subject.MESHMetabolic Clearance Rate/drug effects-
dc.subject.MESHMetabolic Clearance Rate/physiology-
dc.subject.MESHModels, Biological*-
dc.subject.MESHSeasons*-
dc.subject.MESHTetrazoles/administration & dosage*-
dc.subject.MESHTetrazoles/blood*-
dc.titlePopulation pharmacokinetic analysis of diurnal and seasonal variations of plasma concentrations of cilostazol in healthy volunteers.-
dc.typeArticle-
dc.contributor.collegeCollege of Medicine (의과대학)-
dc.contributor.departmentDept. of Pharmacology (약리학)-
dc.contributor.googleauthorDonghwan Lee-
dc.contributor.googleauthorHankil Son-
dc.contributor.googleauthorLay A. Lim-
dc.contributor.googleauthorKyungsoo Park-
dc.identifier.doi10.1097/FTD.0000000000000077-
dc.admin.authorfalse-
dc.admin.mappingfalse-
dc.contributor.localIdA01422-
dc.contributor.localIdA01999-
dc.relation.journalcodeJ02721-
dc.identifier.eissn1536-3694-
dc.identifier.pmid24739664-
dc.subject.keywordpopulation model-
dc.subject.keyworddiurnal variation-
dc.subject.keywordseasonal variation-
dc.subject.keywordcilostazol pharmacokinetics-
dc.subject.keywordoptimal dosing time-
dc.subject.keywordtherapeutic drug monitoring-
dc.contributor.alternativeNamePark, Kyung Soo-
dc.contributor.alternativeNameSon, Han kil-
dc.contributor.affiliatedAuthorPark, Kyung Soo-
dc.contributor.affiliatedAuthorSon, Han kil-
dc.citation.volume36-
dc.citation.number6-
dc.citation.startPage771-
dc.citation.endPage780-
dc.identifier.bibliographicCitationTHERAPEUTIC DRUG MONITORING, Vol.36(6) : 771-780, 2014-
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Pharmacology (약리학교실) > 1. Journal Papers

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