Clonazepam disposition in pediatric patients.
Plasma clonazepam (CZP) and its metabolite [7-aminoclonazepam (7ACZP) and 7-acetamidoclonazepam (7AACZP)] concentrations were measured during a single dosing interval in 10 pediatric epilepsy patients (2-18 years, 11-102 kg) who had been receiving CZP therapeutically from 2 weeks to 4 years. These concentrations were used to determine CZP and metabolite pharmacokinetics. With controlled dosing and postdose sample collection times, large variations were observed in calculated CZP nitroreduction rates [clearance (CL/F) ranged from 7 to 64 ml/h/kg] as well as 7ACZP acetylation rates (CL/F from 10 to 85 ml/h/kg). No 7AACZP (i.e., < 5 ng/ml) was detected by the methods used. Acetylation rates are known to be under genetic control. Further studies are needed to determine whether nitroreduction rates are also under genetic control and whether differences in either of these metabolic rates can explain intraindividual differences in clinical responses observed in CZP-treated patients.
Walson
P D
PD
Department of Pediatrics, Ohio State University and Children's Hospital, Columbus 43205-2696, USA.
Edge
J H
JH
D000107:Acetylation; D000293:Adolescent; D000927:Anticonvulsants / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001711:Biotransformation; D002648:Child; D002675:Child, Preschool; D002998:Clonazepam / Q000493:pharmacokinetics* / Q000627:therapeutic use; D004827:Epilepsy / Q000188:drug therapy; D005260:Female; D006801:Humans; D008297:Male; D010084:Oxidation-Reduction
D000927:Anticonvulsants; D002998:Clonazepam