Clin Ther. 2015 Feb 1;37(2):439-47. doi: 10.1016/j.clinthera.2014.09.022. Epub 2014 Oct 23.

Tolerability and pharmacokinetics of two formulations of megestrol acetate under fed conditionsin healthy volunteers.

Kim YH, Choi HY, Jin S, Noh YH, Kim MJ, Park HJ, Lim HS, Bang K, Lee SH, Bae KS.

Abstract

PURPOSE:

Megestrol acetate oral suspension is an appetite stimulant indicated for cachexia. It is available in a conventional formulation and as a nanocrystal dispersion. The aim of this study was to compare the tolerability and pharmacokinetics of these formulations under fedconditions in healthy Korean volunteers.

METHODS: This was a randomized, single-dose, 3-treatment, 3-period, 6-sequence, crossover study in healthy Korean volunteers. In each period, participants received single oral doses of conventional formulation 800 mg/20 mL (reference), nanocrystal dispersion 650 mg/5.2 mL (test 1), and nanocrystal dispersion 675 mg/5.4 mL (test 2) after a high-calorie, high-fat meal. The periods were separated by a washout period of 14 days. Serial blood samples were collected up to 120 hours after dosing. The plasma concentrations of megestrol acetate were determined with a validated LC-MS/MS method. Pharmacokinetic parameters were obtained by noncompartmental analysis. Tolerability was assessed by physical examinations, vital signs, clinical laboratory test results, and electrocardiograms.

FINDINGS: Thirty-eight healthy volunteers completed the study. The geometric mean ratios of the AUC(last) and C(max) for test 1/reference were 0.88 (90% CI, 0.84-0.92) and 1.07 (90% CI, 0.99-1.15), respectively. The geometric mean ratios of the AUC(last) and C(max) for test 2/reference were 0.88 (90% CI, 0.84-0.93) and1.03 (90% CI, 0.96-1.10), respectively. All formulations were well tolerated.

IMPLICATIONS: The pharmacokinetic characteristics and tolerability of the 2 megestrol acetate formulations are similar in fed volunteers and suggest no relevant difference in tolerability. ClinicalTrials.gov identifier: NCT01342055.

Copyright © 2015 Elsevier HS Journals, Inc. All rights reserved.

KEYWORDS:

healthy; megestrol acetate; nanocrystal dispersion; pharmacokinetics

PMID:

25450470

DOI:

10.1016/j.clinthera.2014.09.022