PLASMA CONCENTRATIONS OF DIAZEPAM AND N‐DESMETHYLDIAZEPAM IN NEWBORN INFANTS AFTER INTRAVENOUS, INTRAMUSCULAR, RECTAL AND ORAL ADMINISTRATION

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Abstract
Newborn infants [5] (birth wt 2900-3600 g) were given diazepam (Valium, LaRoche) for convulsive disorders in 4 equal doses i.v., i.m., rectally and orally with at least 24 h intervals. Three infants were given doses of 1 mg diazepam/kg body wt, and 2 0.5 mg/kg. The parenteral solution of the drug was given i.v., i.m. and rectally. Powder of tablets was given orally. After i.v. administration very high peak values of plasma-diazepam concentration were obtained (5775-10,800 mg/ml after 1 mg/kg, 2750 and 6450 ng/ml after 0.5 mg/kg). Next to i.v. administration rectal administration caused the most rapid increase in plasma-diazepam concentration. Presumed anticonvulsive concentrations (150-300 ng/ml) were obtained within 5 min with 1 mg/kg as well as 0.5 mg/kg rectally. Rectal administration therefore could be a suitable treatment for seizures in the newborn infant. Accumulation of the main depressive metabolite N-desmethyldiazepam occurred in all infants. This phenomenon must be taken into account when repeated doses of diazepam are administered.