Effect of food on the pharmacokinetics of lurasidone: results of two randomized, open-label, crossover studies

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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.

Conclusion

Lurasidone should be administered with food—at least 350 kcal—to ensure maximum exposure. Copyright © 2013 John Wiley & Sons, Ltd.

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