PMID- 27191767 OWN - NLM STAT- MEDLINE DCOM- 20170110 LR - 20221207 IS - 0946-1965 (Print) IS - 0946-1965 (Linking) VI - 54 IP - 9 DP - 2016 Sep TI - Pharmacokinetics of a nanocrystal-containing megestrol acetate formulation: a single-dose, randomized, open-label, 2-part, 2-period crossover study in healthy Korean subjects. PG - 698-704 LID - 10.5414/CP202574 [doi] AB - 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. FAU - Chae, Dong Woo AU - Chae DW FAU - Son, Hankil AU - Son H FAU - Guk, Jinju AU - Guk J FAU - Park, Changhun AU - Park C FAU - Park, Kyungsoo AU - Park K LA - eng SI - ClinicalTrials.gov/NCT02446353 PT - Comparative Study PT - Journal Article PT - Randomized Controlled Trial PL - Germany TA - Int J Clin Pharmacol Ther JT - International journal of clinical pharmacology and therapeutics JID - 9423309 RN - 0 (Appetite Stimulants) RN - 0 (Drugs, Generic) RN - TJ2M0FR8ES (Megestrol Acetate) SB - IM MH - Adult MH - Appetite Stimulants/administration & dosage/*pharmacokinetics MH - Area Under Curve MH - Asian People MH - Biological Availability MH - Cross-Over Studies MH - Drug Delivery Systems MH - Drugs, Generic/administration & dosage/adverse effects/*pharmacokinetics MH - Fasting MH - Humans MH - Male MH - Megestrol Acetate/administration & dosage/adverse effects/*pharmacokinetics MH - Middle Aged MH - *Nanoparticles MH - Therapeutic Equivalency MH - Young Adult EDAT- 2016/05/19 06:00 MHDA- 2017/01/11 06:00 CRDT- 2016/05/19 06:00 PHST- 2016/08/17 00:00 [accepted] PHST- 2016/05/19 06:00 [entrez] PHST- 2016/05/19 06:00 [pubmed] PHST- 2017/01/11 06:00 [medline] AID - 14421 [pii] AID - 10.5414/CP202574 [doi] PST - ppublish SO - Int J Clin Pharmacol Ther. 2016 Sep;54(9):698-704. doi: 10.5414/CP202574.