The impact of total calories and fat content on steady-state serum ziprasidone concentrations in patients receiving oral ziprasidone

Abstract

Food increases the bioavailability of ziprasidone. This study explored the effect of calorie intake and fat content of food on ziprasidone bioavailability in a randomized, 6-way crossover study in 15 patients taking oral ziprasidone 80 mg bid as their standard antipsychotic therapy. There were 6 randomized meal conditions (fasted, low-calorie/low-fat, low-calorie/high-fat, medium-calorie/high-fat, high-calorie/low-fat, and high-calorie/high-fat); each crossover period was separated by at least 3 days for washout of the previous meal condition. Serial blood samples were obtained over the 12 hours post-dose. Pharmacokinetic parameters were calculated by noncompartmental methods. Maximum exposures were observed with medium-calorie and high-calorie meals and were about twice that observed under fasting conditions. The medium-calorie meal (ie, 500 calories) was associated with exposures within approximately 5% (within the equivalence limits of 90% CI) of the high-calorie meals (1000 calories). Low-calorie meals (250 calories) were associated with exposures that were substantially lower (approximately 60% to 90% lower) than those of medium-calorie and high-calorie meals, and approached exposures seen under fasting conditions. The ziprasidone exposures under medium-calorie and high-calorie meals had less variability than those of under low calorie and fasting conditions. In conclusion, ziprasidone exposure did not vary with the fat content (high or low) of a meal and a medium-calorie meal produced near maximal exposures.