Pharmacokinetics of a nanocrystal-containing megestrol acetate formulation: a single-dose, randomized, open-label, 2-part, 2-period crossover study in healthy Korean subjects
| Autor: | Jinju Guk, Hankil Son, Kyungsoo Park, Changhun Park, Dongwoo Chae |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
Adult
Male medicine.medical_specialty Urology Cmax Appetite Stimulants Biological Availability Bioequivalence 030226 pharmacology & pharmacy 03 medical and health sciences Young Adult 0302 clinical medicine Drug Delivery Systems Pharmacokinetics Asian People Medicine Drugs Generic Humans Pharmacology (medical) Pharmacology Cross-Over Studies business.industry Megestrol Acetate Fasting Middle Aged Crossover study Confidence interval Bioavailability Therapeutic Equivalency Megestrol acetate Area Under Curve Nanoparticles business 030217 neurology & neurosurgery medicine.drug Blood sampling |
| Zdroj: | International journal of clinical pharmacology and therapeutics. 54(9) |
| ISSN: | 0946-1965 |
| Popis: | UNLABELLED OBJECTIVE The conventional suspension of megestrol acetate contains micronized megestrol acetate, which was recently discovered to have a disadvantage of decreasing bioavailability when taken in a fasting state. Since megestrol acetate is taken to increase appetite, this property becomes a discouraging factor. To improve upon this, an advanced formulation was developed using a nanocrystal drug-delivery system. This study was conducted to compare the safety and pharmacokinetic characteristics between the conventional formulation of megestrol acetate and a generic version of the advanced formulation containing nanocrystals. METHODS This was a randomized, open-label, 2-period, 2-treatment, crossover, single-dose, 2-part study (part 1 fasting and part 2 fed), conducted in healthy males aged between 20 and 50 years with weight within ± 20% of ideal body weight having no congenital abnormalities or chronic diseases. Different subjects were used in part 1 and part 2, but subjects received a single dose of the reference and test drugs separated by a 14-day washout period. Blood sampling was performed up to 120 hours after dosing using a pre-specified sampling time scheme. Primary pharmacokinetic parameters were Cmax and AUClast of the test and reference formulations of megestrol acetate. Bioequivalence evaluation was based on the standard criterion of 80 - 125% for the 90% confidence interval of geometric mean ratios of test to reference drugs calculated for the pharmacokinetic parameters. To monitor adverse events, both subject interviews and physical examinations were done on a regular time basis. RESULTS 80 subjects (n = 40 each part) were enrolled, and 79 completed the study. The 90% CIs of the geometric mean ratios of Cmax and AUClast were 4.4625 - 5.6018 and 1.3602 - 1.6418, respectively, for part 1, and 0.9793 - 1.1327 and 0.7721 - 0.8431, respectively, for part 2. No significant difference was discovered in the incidence of adverse events (AEs) when test and reference treated groups were compared. CONCLUSIONS Our findings suggest that the test formulation of megestrol-acetate-containing nanocrystals is better absorbed and has higher bioavailability compared to the reference formulation in a fasting state. This should allow for a lower dose and better patient compliance. ClinicalTrials.gov identifier: NCT02446353. |
| Databáze: | OpenAIRE |
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