Clonazepam pharmacokinetics and therapeutic efficacy in neonatal seizures

Eur J Clin Pharmacol. 1986;30(5):585-9. doi: 10.1007/BF00542419.

Abstract

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.

MeSH terms

  • Adult
  • Clonazepam / administration & dosage
  • Clonazepam / metabolism
  • Clonazepam / therapeutic use*
  • Female
  • Half-Life
  • Humans
  • Infant, Newborn
  • Infusions, Intravenous
  • Kinetics
  • Male
  • Seizures / congenital
  • Seizures / drug therapy*

Substances

  • Clonazepam