title: Novel nanocrystal formulation of megestrol acetate has improved bioavailability compared with the conventional micronized formulation in the fasting state.
abstract: BACKGROUND
  Megestrol acetate is an effective treatment for improving appetite and increasing body weight in patients with cancer-associated anorexia. However, Megace oral suspension (OS), a micronized formulation of megestrol acetate, has low bioavailability in the fasting state. To overcome this limitation, a nanocrystal formulation has been developed. This study was performed to evaluate the pharmacokinetics and tolerability of the nanocrystal formulation and to compare them with those of Megace OS in the fed and fasting states.
  
  
  METHODS
  A randomized, open-label, two-treatment, two-period, two-sequence, crossover study was performed in three parts in 93 healthy subjects. A single 625 mg/5 mL oral dose of a nanocrystal formulation was administered in the fasting and fed states (part I). In parts II and III, a single 625 mg/5 mL oral dose of the nanocrystal formulation or Megace OS 800 mg/20 mL was given in the fed and fasting states, respectively. Blood samples were collected for up to 120 hours post dose for pharmacokinetic analysis. Tolerability was evaluated throughout the entire study period.
  
  
  RESULTS
  The nanocrystal formulation of megestrol acetate was rapidly absorbed in both the fed and fasting states. In the fed state, systemic exposure was comparable between the nanocrystal formulation of megestrol acetate and Megace OS. In the fasting state, however, the peak plasma concentration and area under the plasma concentration-time curve to the last measurable concentration of megestrol acetate was 6.7-fold and 1.9-fold higher, respectively, for the nanocrystal formulation than for Megace OS. No serious adverse events were reported.
  
  
  CONCLUSIONS
  Systemic exposure to megestrol acetate is less affected by lack of concomitant food intake when it is administered using the nanocrystal formulation. The nanocrystal formulation of megestrol acetate could be more effective in treating patients with cachexia or anorexia.
authors.affiliation: Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, Republic of Korea.
authors.forename: Kyungho
authors.initials: K
authors.lastname: Jang
authors.affiliation: Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, Republic of Korea.
authors.forename: Seonghae
authors.initials: S
authors.lastname: Yoon
authors.affiliation: Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, Republic of Korea.
authors.forename: Sung-Eun
authors.initials: SE
authors.lastname: Kim
authors.affiliation: Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, Republic of Korea.
authors.forename: Joo-Youn
authors.initials: JY
authors.lastname: Cho
authors.affiliation: Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, Republic of Korea.
authors.forename: Seo Hyun
authors.initials: SH
authors.lastname: Yoon
authors.affiliation: Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, Republic of Korea.
authors.forename: Kyoung Soo
authors.initials: KS
authors.lastname: Lim
authors.affiliation: Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, Republic of Korea.
authors.forename: Kyung-Sang
authors.initials: KS
authors.lastname: Yu
authors.affiliation: Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, Republic of Korea.
authors.forename: In-Jin
authors.initials: IJ
authors.lastname: Jang
authors.affiliation: Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, Republic of Korea.
authors.forename: Howard
authors.initials: H
authors.lastname: Lee
mesh_terms: D000328:Adult; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical; D018592:Cross-Over Studies; D004361:Drug Tolerance; D005215:Fasting; D064368:Healthy Volunteers; D006801:Humans; D008297:Male; D019290:Megestrol Acetate / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry* / Q000493:pharmacokinetics*; D008875:Middle Aged; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry*; D055815:Young Adult
chemical_list: D019290:Megestrol Acetate
keywords: anorexia; food; megestrol acetate; nanocrystal formulation