Quantitative Assessment of Food Effect on the Pharmacokinetics of Nano‐Crystallized Megestrol Acetate
| Autor: | Jinju Guk, Dongwoo Chae, Kyungsoo Park, Hankil Son |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
Adult
Male Cachexia media_common.quotation_subject Cmax Administration Oral Appetite Stimulants Biological Availability Absorption (skin) Pharmacology Toxicology Models Biological 030226 pharmacology & pharmacy Eating Food-Drug Interactions Young Adult 03 medical and health sciences Drug Delivery Systems 0302 clinical medicine Pharmacokinetics Republic of Korea medicine Humans Drug Dosage Calculations media_common Cross-Over Studies Chemistry Megestrol Acetate Appetite Fasting General Medicine Crossover study Healthy Volunteers NONMEM Bioavailability 030220 oncology & carcinogenesis Megestrol acetate Nanoparticles medicine.drug |
| Zdroj: | Basic & Clinical Pharmacology & Toxicology. 120:270-277 |
| ISSN: | 1742-7843 1742-7835 |
| DOI: | 10.1111/bcpt.12677 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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