THE EFFECT OF TIMING OF A STANDARD MEAL ON THE PHARMACOKINETICS AND PHARMACODYNAMICS OF THE NOVEL ATYPICAL ANTIPSYCHOTIC AGENT ZIPRASIDONE

Study Objective. To evaluate the influence of a high-fat meal on the p harmacokinetics and pharmacodynamics of the novel atypical antipsychot ic drug ziprasidone. Design. Open, randomized, three-way crossover stu dy. Setting. University-based research facility. Subjects. Eight healt hy male volunteers. Interventions. Ziprasidone 20 mg was administered under fasting conditions (treatment A), and directly after (treatment B) and 2 hours after (treatment C) a standard high-fat breakfast. Meas urements and Main Results. Serial blood samples were obtained over 36 hours. Three objective psychometric tests were employed to evaluate da ytime vigilance at baseline and 2 hours after each dose. Ziprasidone h ad a significant effect on area under the curve (AUC(0-infinity)), max imum serum concentration, and half-life (analysis of variance all p<0. 05), with the mean AUC(0-infinity) being significantly greater (627.2 +/- 206.4 vs 371.0 +/- 126.5 ng.hr/ml, ANOVA with Bonferroni's criteri a p<0.016) and half-life Significantly shorter (4.7 +/- 0.8 vs 6.6 +/- 1.3 hrs, ANOVA with Bonferroni's criteria p<0.016) after treatment B compared with treatment A. Although similar trends were observed after treatment C compared with treatment A, the differences did not reach statistical significance when Bonferroni's correction criteria were ap plied (p>0.016). Conclusion. These data suggest an increase in systemi c exposure to the highly lipophilic compound ziprasidone when taken af ter fatty foods, possibly due to improved drug dissolution and solubil ization. The drug's longer half-life under fasting conditions may refl ect dissolution-limited absorption, although this could not be directl y assessed. Despite postprandial increases in ziprasidone AUC(0-infini ty) and maximum concentration, daytime vigilance was not affected.