Use of population pharmacokinetic modeling to characterize intramuscular pharmacokinetics for ziprasidone in schizophrenic patients

Objective: To characterize the pharmacokinetics (PK) of the rapid-acting intramuscular (IM) formulation of the novel antipsychotic ziprasidone in schizophrenic patients. Methods: Building upon a population PK model established from data-rich, single-dose studies performed in healthy subjects, the multiple-dose disposition of ziprasidone was characterized in patients receiving ziprasidone IM dose of 5mg (n=6), 10mg (n=6), and 20 mg (n=6) administered four times daily for three days. PK sampling was limited to 12 samples on Day 1 and 14 on Day 3. Results: The results were consistent with predictions from single dose, showing attainment of peak exposure within approx 30 min, dose related increases in exposure, and little drug accumulation. Conclusions: The approach used here demonstrated that population PK modeling is a useful tool in understanding drug disposition where PK sampling is limited. Ziprasidone IM has a predictable, linear PK profile. Therapeutic plasma levels are attained rapidly.