The impact of calories and fat content of meals on oral ziprasidone absorption: a randomized, open-label, crossover trial.
BACKGROUND
Food is known to increase the bioavailability of ziprasidone. Therefore, we evaluated the effects of meals of differing caloric and fat content on steady-state ziprasidone exposure in a stable, treated group of subjects with DSM-IV diagnoses of schizophrenia, schizoaffective disorder, bipolar disorder, or psychotic disorder (not otherwise specified) who were already receiving oral ziprasidone as their standard therapy.


METHODS
Patients took ziprasidone under 6 meal conditions in randomized sequences (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 postdose. The study was conducted from July 27 to September 28 of 2006.


RESULTS
Maximum ziprasidone exposures in this study were observed with high-calorie meals (1000 kcal), which were nearly twice those observed under fasting conditions. The medium-calorie meal (500 kcal) was associated with exposures similar to the high-calorie meals. Low-calorie meals (250 kcal) were associated with exposures that were approximately 60% to 90% lower than those of medium- and high-calorie meals, and approached exposures seen under fasting conditions. Fat content of the meal had no significant effect on ziprasidone absorption. The ziprasidone exposures observed with medium- and high-calorie meals had less variability than those with low-calorie meals and under fasting conditions.


CONCLUSIONS
These results confirm that ziprasidone should be taken with food and that a meal equal to or greater than 500 kcal, irrespective of fat content, is required for optimal and reproducible bioavailability of the administered dose.
Gandelman
Kuan
K
Clinical Pharmacology, Pfizer Inc, New York, NY 10017, USA. kuan.gandelman@pfizer.com
Alderman
Jeffrey A
JA
Glue
Paul
P
Lombardo
Ilise
I
LaBadie
Robert R
RR
Versavel
Mark
M
Preskorn
Sheldon H
SH
D000328:Adult; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000819:agonists / Q000493:pharmacokinetics*; D001682:Biological Availability; D001714:Bipolar Disorder / Q000097:blood* / Q000188:drug therapy; D018592:Cross-Over Studies; D004041:Dietary Fats / Q000378:metabolism*; D004334:Drug Administration Schedule; D002149:Energy Intake / Q000502:physiology*; D005260:Female; D018565:Food-Drug Interactions; D006801:Humans; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D011618:Psychotic Disorders / Q000097:blood* / Q000188:drug therapy; D012559:Schizophrenia / Q000097:blood* / Q000188:drug therapy; D013844:Thiazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D055815:Young Adult
D014150:Antipsychotic Agents; D004041:Dietary Fats; D010879:Piperazines; D013844:Thiazoles; C092292:ziprasidone