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Quantitative Assessment of Food Effect on the Pharmacokinetics of Nano-Crystallized Megestrol Acetate

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dc.contributor.author박경수-
dc.contributor.author채동우-
dc.date.accessioned2017-11-02T08:12:51Z-
dc.date.available2017-11-02T08:12:51Z-
dc.date.issued2017-
dc.identifier.issn1742-7835-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/154207-
dc.description.abstractMegestrol acetate, an appetite stimulant with low bioavailability, shows increased bioavailability when taken together with food. However, the pharmacokinetic characteristics of megestrol acetate and its relation with food are not well understood. This study aimed to investigate the food effect on the pharmacokinetics (PK) of the recently developed nano-crystallized megestrol acetate (NCMA), using a model-based approach. Data were obtained from an NCMA PK study consisting of a single dose in fasting (39 individuals) and fed conditions (40 individuals). Plasma concentrations were measured up to 120 hr after dosing. With the incorporation of body-weight via allometry, NONMEM 7.3 was used to develop a PK model, which was then used to simulate an optimal fasting dose yielding an area under concentration (AUC) and maximum concentration (Cmax ) of NCMA close to those obtained with the fed dose. NCMA concentrations were best characterized by a two-compartment model with first-order absorption linked to a recycling compartment to account for the multiple concentration peaks observed. Food increased bioavailability 2.2 times and decreased the absorption rate constant 0.58 times. Recycling event times were estimated to be 3.56, 7.99 and 24.0 hr. The optimal fast dose was 2.0 times higher than the fed dose, and the resulting difference in drug exposure between the fasting and fed dose was 7.5%. This work suggests that the PK model developed can be applied to an optimal dosage regimen design for NCMA treatment.-
dc.description.statementOfResponsibilityrestriction-
dc.publisherBlackwell-
dc.relation.isPartOfBasic & Clinical Pharmacology & Toxicology-
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.MESHAppetite Stimulants/administration & dosage*-
dc.subject.MESHAppetite Stimulants/pharmacokinetics*-
dc.subject.MESHAppetite Stimulants/therapeutic use-
dc.subject.MESHBiological Availability-
dc.subject.MESHCachexia/drug therapy-
dc.subject.MESHCross-Over Studies-
dc.subject.MESHDrug Delivery Systems/methods-
dc.subject.MESHDrug Dosage Calculations-
dc.subject.MESHEating-
dc.subject.MESHFasting-
dc.subject.MESHFood-Drug Interactions*-
dc.subject.MESHHealthy Volunteers-
dc.subject.MESHHumans-
dc.subject.MESHMale-
dc.subject.MESHMegestrol Acetate/administration & dosage*-
dc.subject.MESHMegestrol Acetate/pharmacokinetics*-
dc.subject.MESHMegestrol Acetate/therapeutic use-
dc.subject.MESHModels, Biological*-
dc.subject.MESHNanoparticles-
dc.subject.MESHRepublic of Korea-
dc.subject.MESHYoung Adult-
dc.titleQuantitative Assessment of Food Effect on the Pharmacokinetics of Nano-Crystallized Megestrol Acetate-
dc.typeArticle-
dc.publisher.locationEngland-
dc.contributor.collegeCollege of Medicine-
dc.contributor.departmentDept. of Pharmacology-
dc.contributor.googleauthorJinju Guk-
dc.contributor.googleauthorHankil Son-
dc.contributor.googleauthorDong Woo Chae-
dc.contributor.googleauthorKyungsoo Park-
dc.identifier.doi10.1111/bcpt.12677-
dc.contributor.localIdA04014-
dc.contributor.localIdA01422-
dc.relation.journalcodeJ00271-
dc.relation.journalsince2004~-
dc.identifier.pmid27639080-
dc.identifier.urlhttp://onlinelibrary.wiley.com/doi/10.1111/bcpt.12677/abstract-
dc.relation.journalbefore~2003 Pharmacology & Toxicology-
dc.contributor.alternativeNamePark, Kyung Soo-
dc.contributor.alternativeNameChae, Dong Woo-
dc.contributor.affiliatedAuthorChae, Dong Woo-
dc.contributor.affiliatedAuthorPark, Kyung Soo-
dc.citation.titleBasic & Clinical Pharmacology & Toxicology-
dc.citation.volume120-
dc.citation.number3-
dc.citation.startPage270-
dc.citation.endPage277-
dc.identifier.bibliographicCitationBasic & Clinical Pharmacology & Toxicology, Vol.120(3) : 270-277, 2017-
dc.date.modified2017-11-01-
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Pharmacology (약리학교실) > 1. Journal Papers

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