Effect of hyperbilirubinemia on the pharmacokinetics of diazepam in the rat.
The pharmacokinetics of intravenously-administered diazepam have been studied in heterozygous (non-jaundiced) and homozygous (jaundiced) Gunn rats following single doses of 10 mg/Kg. Plasma concentration time course data from heterozygous and homozygous animals can be described adequately by biexponential equations. A faster plasma clearance rate (Clp) and shorter elimination half life (t 1/2) as well as reduced volumes of distribution [Vp and Vd(area)] were observed in homozygous animals. These potential effects of bilirubin on the distribution and elimination of diazepam should be considered if diazepam is to be used in the therapy of neonatal hyperbilirubinemia.
D000818:Animals; D003975:Diazepam / Q000097:blood / Q000378:metabolism*; D004195:Disease Models, Animal; D006207:Half-Life; D006801:Humans; D006932:Hyperbilirubinemia / Q000378:metabolism*; D006933:Hyperbilirubinemia, Hereditary / Q000378:metabolism; D007231:Infant, Newborn; D007567:Jaundice, Neonatal / Q000378:metabolism; D007700:Kinetics; D008297:Male; D051381:Rats; D013997:Time Factors
D003975:Diazepam