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Clonazepam pharmacokinetics and therapeutic efficacy in neonatal seizures

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Summary

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.

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André, M., Boutroy, M.J., Dubruc, C. et al. Clonazepam pharmacokinetics and therapeutic efficacy in neonatal seizures. Eur J Clin Pharmacol 30, 585–589 (1986). https://doi.org/10.1007/BF00542419

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  • DOI: https://doi.org/10.1007/BF00542419

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