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

被引:29
作者
Sallee, Floyd R.
Miceli, Jeffrey J.
Tensfeldt, Thomas
Robarge, Lisa
Wilner, Keith
Patel, Nick C.
机构
[1] Univ Cincinnati, Coll Med, Dept Psychiat, Cincinnati, OH 45267 USA
[2] Univ Cincinnati, Coll Pharm, Dept Psychiat, Cincinnati, OH 45267 USA
[3] CNS Clin Pfizer Global Res & Dev, Groton, CT USA
[4] Pfizer Global Res & Dev, Dept Clin Res, San Diego, CA USA
关键词
ziprasidone; Tourette's disorder; pharmacokinetics; safety;
D O I
10.1097/01.chi.0000215347.93902.3e
中图分类号
B844 [发展心理学(人类心理学)];
学科分类号
040202 ;
摘要
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 C-max 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 QTc 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.
引用
收藏
页码:720 / 728
页数:9
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