The Effect of Food on the Absorption of Oral Ziprasidone

Oral ziprasidone bioavailability is increased when taken with food. Here we describe two pharmacokinetic studies to quantify the impact of food on ziprasidone absorption in healthy volunteers. The first, an open-label, six-way crossover study, investigated ziprasidone absorption in eight healthy men. Subjects received oral ziprasidone (20, 40, and 80 mg) after an 8-hour fast or immediately following a US Food and Drug Administration standard meal (50% fat). In this study, area under the serum concentration-time curve (AUC) was greater in fed than in fasting states at each dose (20 mg, +48%; 40 mg, +87%; 80 mg, +101%). Under fasting conditions, increases in AUC and maximum drug concentration (C(max)) were less than dose-proportional; under fed conditions, they were dose-proportional. The second, 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 (30% fat) meal. AUC and C(max) under fed conditions increased by 104% and 84% (60%-fat meal) and 79% and 98% (30%-fat meal), respectively, relative to the fasting state. There was no clear difference in ziprasidone bioavailability between the fed groups, suggesting that meal fat content is not a major determinant of bioavailability. Less pharmacokinetic variability was observed in the fed state, suggesting more consistent absorption of ziprasidone. These results demonstrate that administration of ziprasidone with food is crucial to ensure optimal, reliable dose-dependent bioavailability and thus predictable symptom control and tolerability. Psychopharmacology Bulletin. 2007;40(3):58-68.