title: Effect of food on the pharmacokinetics of lurasidone: results of two randomized, open-label, crossover studies.
abstract: OBJECTIVE
  This study aimed to investigate the effect of prandial status and caloric and fat composition of meals on the pharmacokinetics of lurasidone.
  
  
  METHODS
  Two randomized, open-label, crossover studies were conducted in clinically stable adults with schizophrenia or schizoaffective disorder. Study 1 (n = 16) evaluated the effect of fasting and three meal types (100 kcal/medium fat, 200 kcal/medium fat, and 800-1000 kcal/high fat), and Study 2 (n = 26) evaluated the effect of fasting and five meal types (350 kcal/high fat, 500 kcal/low fat, 500 kcal/high fat, 800-1000 kcal/low fat, and 800-1000 kcal/high fat) on the bioavailability of lurasidone. Subjects received lurasidone 120 mg once daily. Maximum serum concentration (Cmax ) and area under the serum concentration-time curve over the dosing interval (AUC0-tau ) were determined on Day 5 for each meal type.
  
  
  RESULTS
  In Study 1, the geometric mean Cmax in the fasted state was 56.7 ng/mL compared with 123.0 ng/mL for the 800- to 1000-kcal meal; mean AUC0-tau was 360.0 versus 752.4 ng·h/mL (both p < 0.001). Lurasidone exposure following meals containing 100 and 200 kcal was substantially lower than with meals containing 800-1000 kcal. In Study 2, the geometric mean Cmax was 52.9 ng/mL in the fasted state, 161 ng/mL for the 350-kcal/high-fat meal, 135 ng/mL for the 500-kcal/high-fat meal, and 131 ng/mL for the 800- to 1000-kcal/high-fat meal; mean AUC0-tau was 390, 743, 727, and 769 ng·h/mL, respectively. For all comparisons, the 90% confidence interval of the fed to fasted ratios indicated nonequivalence. Lurasidone exposure was similar following meals containing 350-1000 kcal and was independent of fat content.
  
  
  CONCLUSIONS
  Lurasidone should be administered with food-at least 350 kcal-to ensure maximum exposure.
authors.affiliation: Clinical Research Institute, Wichita, Kansas, USA.
authors.forename: Sheldon
authors.initials: S
authors.lastname: Preskorn
authors.forename: Larry
authors.initials: L
authors.lastname: Ereshefsky
authors.forename: Yu-Yuan
authors.initials: YY
authors.lastname: Chiu
authors.forename: Nagaraju
authors.initials: N
authors.lastname: Poola
authors.forename: Antony
authors.initials: A
authors.lastname: Loebel
mesh_terms: D000328:Adult; D018592:Cross-Over Studies; D005260:Female; D018565:Food-Drug Interactions / Q000502:physiology*; D006801:Humans; D054833:Isoindoles / Q000008:administration & dosage* / Q000097:blood*; D000069056:Lurasidone Hydrochloride; D008297:Male; D008875:Middle Aged; D012559:Schizophrenia / Q000097:blood* / Q000188:drug therapy*; D013844:Thiazoles / Q000008:administration & dosage* / Q000097:blood*
chemical_list: D054833:Isoindoles; D013844:Thiazoles; D000069056:Lurasidone Hydrochloride
keywords: absorption; food; lurasidone; pharmacokinetics; schizophrenia