Floyd R Sallee1, Jeffrey J Miceli2, Thomas Tensfeldt2, Lisa Robarge2, Keith Wilner2, Nick C Patel2. 1. Dr. Sallee is with the Department of Psychiatry, College of Medicine, and Dr. Patel is with the College of Pharmacy and the Department of Psychiatry, University of Cincinnati; Dr. Miceli, Mr. Tensfeldt, and Ms. Robarge are with CNS Clinical Pfizer Global Research and Development, Groton, CT; Dr. Wilner is with the Department of Clinical Research, Pfizer Global Research and Development, San Diego, CA. Electronic address: floyd.sallee@uc.edu. 2. Dr. Sallee is with the Department of Psychiatry, College of Medicine, and Dr. Patel is with the College of Pharmacy and the Department of Psychiatry, University of Cincinnati; Dr. Miceli, Mr. Tensfeldt, and Ms. Robarge are with CNS Clinical Pfizer Global Research and Development, Groton, CT; Dr. Wilner is with the Department of Clinical Research, Pfizer Global Research and Development, San Diego, CA.
Abstract
OBJECTIVE: The purpose of this study was to provide single-dose pharmacokinetic, safety, and tolerability data for ziprasidone in youths with tic disorder, for comparison to adult studies to discern whether ziprasidone pediatric dosing could be modeled from adult data. METHOD: A single-dose, open-label study of ziprasidone was conducted in youths (ages 7-16 years) with Tourette's disorder or chronic tic disorder. Dosing of ziprasidone oral suspension (40 mg/mL) was weight adjusted: >60 kg, 20 mg (group 1, n = 8); 31 to 60 kg, 10 mg (group 2, n = 8); and 16 to 30 kg, 5 mg (group 3, n = 8). Patients were assessed for serum ziprasidone concentration, safety, tolerability, and electrocardiogram pre- and postdose. RESULTS: Twenty-four patients were evaluated for safety and tolerability, and 23 were evaluated for pharmacokinetics. Regression analysis of AUC(0-infinity) and Cmax values versus weight-normalized dose showed linear, dose-related changes in ziprasidone exposure. Ziprasidone was well tolerated with frequent, although transient, somnolence. No clinically significant change from baseline was observed in Bazett's or Fridericia's corrected QT(c) interval, and change in QT(c) interval was not related to serum ziprasidone concentration. CONCLUSIONS: Oral ziprasidone exhibited linear pharmacokinetics and dose-related exposure in youths with Tourette's disorder or chronic tic disorder, which are comparable to adult data. A single dose of ziprasidone was well tolerated without clinically significant effects on electrocardiograms collected around the time of maximum serum concentration.
OBJECTIVE: The purpose of this study was to provide single-dose pharmacokinetic, safety, and tolerability data for ziprasidone in youths with tic disorder, for comparison to adult studies to discern whether ziprasidone pediatric dosing could be modeled from adult data. METHOD: A single-dose, open-label study of ziprasidone was conducted in youths (ages 7-16 years) with Tourette's disorder or chronic tic disorder. Dosing of ziprasidone oral suspension (40 mg/mL) was weight adjusted: >60 kg, 20 mg (group 1, n = 8); 31 to 60 kg, 10 mg (group 2, n = 8); and 16 to 30 kg, 5 mg (group 3, n = 8). Patients were assessed for serum ziprasidone concentration, safety, tolerability, and electrocardiogram pre- and postdose. RESULTS: Twenty-four patients were evaluated for safety and tolerability, and 23 were evaluated for pharmacokinetics. Regression analysis of AUC(0-infinity) and Cmax values versus weight-normalized dose showed linear, dose-related changes in ziprasidone exposure. Ziprasidone was well tolerated with frequent, although transient, somnolence. No clinically significant change from baseline was observed in Bazett's or Fridericia's corrected QT(c) interval, and change in QT(c) interval was not related to serum ziprasidone concentration. CONCLUSIONS: Oral ziprasidone exhibited linear pharmacokinetics and dose-related exposure in youths with Tourette's disorder or chronic tic disorder, which are comparable to adult data. A single dose of ziprasidone was well tolerated without clinically significant effects on electrocardiograms collected around the time of maximum serum concentration.