title: Tolerability and pharmacokinetics of two formulations of megestrol acetate under fed conditions in healthy volunteers.
abstract: OBJECTIVE
  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 fed conditions 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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Clinical Pharmacology and Therapeutics, College of Medicine, University of Ulsan, Asan Medical Center, Seoul, Republic of Korea.
authors.forename: Yo Han
authors.initials: YH
authors.lastname: Kim
authors.affiliation: Department of Clinical Pharmacology and Therapeutics, College of Medicine, University of Ulsan, Asan Medical Center, Seoul, Republic of Korea.
authors.forename: Hee Youn
authors.initials: HY
authors.lastname: Choi
authors.affiliation: Department of Clinical Pharmacology and Therapeutics, College of Medicine, University of Ulsan, Asan Medical Center, Seoul, Republic of Korea.
authors.forename: Seokjoon
authors.initials: S
authors.lastname: Jin
authors.affiliation: Department of Clinical Pharmacology, Busan Paik Hospital, Busan, Republic of Korea.
authors.forename: Yook-Hwan
authors.initials: YH
authors.lastname: Noh
authors.affiliation: Department of Clinical Pharmacology and Therapeutics, College of Medicine, University of Ulsan, Asan Medical Center, Seoul, Republic of Korea.
authors.forename: Mi Jo
authors.initials: MJ
authors.lastname: Kim
authors.affiliation: Clinical Trial Center, Asan Medical Center, Seoul, Republic of Korea.
authors.forename: Hyun-Jung
authors.initials: HJ
authors.lastname: Park
authors.affiliation: Department of Clinical Pharmacology and Therapeutics, College of Medicine, University of Ulsan, Asan Medical Center, Seoul, Republic of Korea.
authors.forename: Hyeong-Seok
authors.initials: HS
authors.lastname: Lim
authors.affiliation: LG Life Sciences, Ltd., Seoul, Republic of Korea.
authors.forename: Keunsu
authors.initials: K
authors.lastname: Bang
authors.affiliation: LG Life Sciences, Ltd., Seoul, Republic of Korea.
authors.forename: Sung-Hack
authors.initials: SH
authors.lastname: Lee
authors.affiliation: Department of Clinical Pharmacology and Therapeutics, College of Medicine, University of Ulsan, Asan Medical Center, Seoul, Republic of Korea. Electronic address: ksbae@amc.seoul.kr.
authors.forename: Kyun-Seop
authors.initials: KS
authors.lastname: Bae
mesh_terms: D000328:Adult; D019167:Appetite Stimulants / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics*; D019540:Area Under Curve; D044466:Asian People; D002626:Chemistry, Pharmaceutical; D002853:Chromatography, Liquid; D018592:Cross-Over Studies; D064368:Healthy Volunteers; D006801:Humans; D008297:Male; D019290:Megestrol Acetate / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics*; D053758:Nanoparticles / Q000008:administration & dosage / Q000378:metabolism; D053719:Tandem Mass Spectrometry; D013810:Therapeutic Equivalency; D055815:Young Adult
chemical_list: D019167:Appetite Stimulants; D019290:Megestrol Acetate
keywords: healthy; megestrol acetate; nanocrystal dispersion; pharmacokinetics