Cited 5 times in
Population pharmacokinetic analysis of diurnal and seasonal variations of plasma concentrations of cilostazol in healthy volunteers.
DC Field | Value | Language |
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dc.contributor.author | 박경수 | - |
dc.contributor.author | 손한길 | - |
dc.date.accessioned | 2015-12-28T10:56:28Z | - |
dc.date.available | 2015-12-28T10:56:28Z | - |
dc.date.issued | 2014 | - |
dc.identifier.issn | 0163-4356 | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/138352 | - |
dc.description.abstract | BACKGROUND: 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.statementOfResponsibility | open | - |
dc.format.extent | 771~780 | - |
dc.relation.isPartOf | THERAPEUTIC DRUG MONITORING | - |
dc.rights | CC BY-NC-ND 2.0 KR | - |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/2.0/kr/ | - |
dc.subject.MESH | Administration, Oral | - |
dc.subject.MESH | Circadian Rhythm/drug effects | - |
dc.subject.MESH | Circadian Rhythm/physiology* | - |
dc.subject.MESH | Female | - |
dc.subject.MESH | Healthy Volunteers* | - |
dc.subject.MESH | Humans | - |
dc.subject.MESH | Male | - |
dc.subject.MESH | Metabolic Clearance Rate/drug effects | - |
dc.subject.MESH | Metabolic Clearance Rate/physiology | - |
dc.subject.MESH | Models, Biological* | - |
dc.subject.MESH | Seasons* | - |
dc.subject.MESH | Tetrazoles/administration & dosage* | - |
dc.subject.MESH | Tetrazoles/blood* | - |
dc.title | Population pharmacokinetic analysis of diurnal and seasonal variations of plasma concentrations of cilostazol in healthy volunteers. | - |
dc.type | Article | - |
dc.contributor.college | College of Medicine (의과대학) | - |
dc.contributor.department | Dept. of Pharmacology (약리학) | - |
dc.contributor.googleauthor | Donghwan Lee | - |
dc.contributor.googleauthor | Hankil Son | - |
dc.contributor.googleauthor | Lay A. Lim | - |
dc.contributor.googleauthor | Kyungsoo Park | - |
dc.identifier.doi | 10.1097/FTD.0000000000000077 | - |
dc.admin.author | false | - |
dc.admin.mapping | false | - |
dc.contributor.localId | A01422 | - |
dc.contributor.localId | A01999 | - |
dc.relation.journalcode | J02721 | - |
dc.identifier.eissn | 1536-3694 | - |
dc.identifier.pmid | 24739664 | - |
dc.subject.keyword | population model | - |
dc.subject.keyword | diurnal variation | - |
dc.subject.keyword | seasonal variation | - |
dc.subject.keyword | cilostazol pharmacokinetics | - |
dc.subject.keyword | optimal dosing time | - |
dc.subject.keyword | therapeutic drug monitoring | - |
dc.contributor.alternativeName | Park, Kyung Soo | - |
dc.contributor.alternativeName | Son, Han kil | - |
dc.contributor.affiliatedAuthor | Park, Kyung Soo | - |
dc.contributor.affiliatedAuthor | Son, Han kil | - |
dc.citation.volume | 36 | - |
dc.citation.number | 6 | - |
dc.citation.startPage | 771 | - |
dc.citation.endPage | 780 | - |
dc.identifier.bibliographicCitation | THERAPEUTIC DRUG MONITORING, Vol.36(6) : 771-780, 2014 | - |
dc.identifier.rimsid | 49120 | - |
dc.type.rims | ART | - |
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