The Effect of Food on the Absorption of Oral Ziprasidone

Objective: Oral ziprasidone bioavailability is known to increase when taken with food. Two pharmacokinetic studies were conducted to quantify the impact of food on ziprasidone absorption in healthy volunteers.

Study 1: An open-label, six-way crossover study investigated ziprasidone absorption in eight healthy men. Subjects received oral ziprasidone (20, 40, and 80 mg) either after an 8-hour fast or immediately following a US Food and Drug Administration (FDA) standard meal (50% fat). At each dose, the area under the serum concentration–time curve (AUC) was greater in the fed than in the fasting state (20 mg, +48%; 40 mg, +87%; 80 mg, +101%). Under fasting conditions, increases in AUC and maximum drug concentration (Cmax) were less than dose-proportional; under fed conditions, they were dose-proportional.

Study 2: An open-label, randomized, three-way crossover study explored the impact of dietary fat on ziprasidone absorption in 14 healthy subjects. Subjects received ziprasidone (40 mg) under three conditions: fasting, with a high-fat meal (60% fat), and with a moderate-fat meal (30% fat). Relative to fasting, AUC and Cmax increased by 104% and 84% (60% fat meal), and by 79% and 98% (30% fat meal), respectively. There was no clear difference in bioavailability between the fed groups, suggesting that meal fat content is not a major determinant of absorption.

Key Findings: Less pharmacokinetic variability was observed in the fed state, suggesting more consistent absorption of ziprasidone when taken with food.

Conclusion: Administration of ziprasidone with food is crucial to ensure optimal, reliable, dose-dependent bioavailability and, therefore, predictable symptom control and tolerability.

Psychopharmacology Bulletin. 2007;40(3):58–68.