Single-dose pharmacokinetics and safety of ziprasidone in children and adolescents.
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.


METHODS
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.
Sallee
Floyd R
FR
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.
Miceli
Jeffrey J
JJ
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.
Tensfeldt
Thomas
T
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.
Robarge
Lisa
L
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.
Wilner
Keith
K
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.
Patel
Nick C
NC
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.
D000293:Adolescent; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002648:Child; D016000:Cluster Analysis; D004305:Dose-Response Relationship, Drug; D004562:Electrocardiography; D005260:Female; D006801:Humans; D008297:Male; D010879:Piperazines / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D013844:Thiazoles / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D005879:Tourette Syndrome / Q000175:diagnosis / Q000188:drug therapy*
D014150:Antipsychotic Agents; D010879:Piperazines; D013844:Thiazoles; C092292:ziprasidone