title: Plasma concentrations of diazepam and N-desmethyldiazepam in newborn infants after intravenous, intramuscular, rectal and oral administration.
abstract: Five newborn infants (birth weight 2900--3600 g) were given diazepam (Valium, LaRoche) for convulsive disorders in 4 equal doses intravenously, intramuscularly, rectally and orally with at least 24 hours intervals. Three infants were given doses of 1 mg diazepam/kg body weight, and 2 0.5 mg/kg. The parenteral solution of the drug was given intravenously, intramuscularly and rectally. Powder of tablets was given orally. After intravenous administration very high peak values of plasma-diazepam concentration were obtained (5775--10800 ng/ml after 1 mg/kg, 2750 and 6450 ng/ml after 0.5 mg/kg). Next to intravenous administration rectal administration caused the most rapid increase in plasma-diazepam concentration. Presumed anticonsulsive 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.
mesh_terms: D000284:Administration, Oral; D003975:Diazepam / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D007232:Infant, Newborn, Diseases / Q000188:drug therapy; D007273:Injections, Intramuscular; D007275:Injections, Intravenous; D003708:Nordazepam / Q000097:blood*; D011247:Pregnancy; D012007:Rectum; D012640:Seizures / Q000097:blood / Q000188:drug therapy; D013997:Time Factors
chemical_list: D003708:Nordazepam; D003975:Diazepam