Clonazepam pharmacokinetics and therapeutic efficacy in neonatal seizures.
Eighteen newborns (gestational age 28 to 42 weeks and post-natal age 0.5 to 44 days) suffering from convulsions not controlled by phenobarbital were treated with clonazepam 0.1 mg/kg (8 cases) or 0.2 mg/kg (10 cases) administered by slow intravenous infusion. The plasma half-lives in these "phenobarbital pretreated neonates' were of the same order of magnitude as those reported in adults (20-43 h). Post-natal age did affect clearance, which was 50-70% less than in adults and older children. At the end of the infusion period, plasma clonazepam ranged from 28 to 117 ng/ml in the 0.1 mg/kg group and from 99 to 380 ng/ml in the 0.2 mg/kg group. In the former an immediate therapeutic response was observed in 7 out of 8 cases, and in the latter a significant and somehow delayed effect on convulsion was present only in 6 cases. The data suggest that optimal therapeutic response might already have been achieved with the 0.1 mg/kg dose. Higher doses and toxic concentrations of clonazepam may be detrimental to complete control of seizures and may expose the newborn to an unnecessary risk of adverse events.
D000328:Adult; D002998:Clonazepam / Q000008:administration & dosage / Q000378:metabolism / Q000627:therapeutic use*; D005260:Female; D006207:Half-Life; D006801:Humans; D007231:Infant, Newborn; D007262:Infusions, Intravenous; D007700:Kinetics; D008297:Male; D012640:Seizures / Q000151:congenital / Q000188:drug therapy*
D002998:Clonazepam