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

 Jinju Guk  ;  Hankil Son  ;  Dong Woo Chae  ;  Kyungsoo Park 
 Basic & Clinical Pharmacology & Toxicology, Vol.120(3) : 270-277, 2017 
Journal Title
 Basic & Clinical Pharmacology & Toxicology 
Issue Date
Administration, Oral ; Adult ; Appetite Stimulants/administration & dosage* ; Appetite Stimulants/pharmacokinetics* ; Appetite Stimulants/therapeutic use ; Biological Availability ; Cachexia/drug therapy ; Cross-Over Studies ; Drug Delivery Systems/methods ; Drug Dosage Calculations ; Eating ; Fasting ; Food-Drug Interactions* ; Healthy Volunteers ; Humans ; Male ; Megestrol Acetate/administration & dosage* ; Megestrol Acetate/pharmacokinetics* ; Megestrol Acetate/therapeutic use ; Models, Biological* ; Nanoparticles ; Republic of Korea ; Young Adult
Megestrol 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.
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1. College of Medicine (의과대학) > Dept. of Pharmacology (약리학교실) > 1. Journal Papers
Yonsei Authors
박경수(Park, Kyungsoo) ORCID logo https://orcid.org/0000-0002-6972-1143
채동우(Chae, Dong Woo) ORCID logo https://orcid.org/0000-0002-7675-3821
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