Effect of hyperbilirubinemia on the pharmacokinetics of pentobarbital in the rat.

The pharmacokinetics of intravenously administered pentobarbitol have been studied in heterozygous (non-jaundiced) and homozygous (jaundiced) Gunn rats following single doses of 30 mg/Kg. Plasma pentobarbital concentration time course data from heterozygous animals were fitted to a biexponential equation while a triexponential equation was required to fit the data from homozygous animals. A slower plasma clearance rate and longer elimination half-life were observed in homozygous animals as well as increased overall volumes of pentobarbital distribution. These results suggest a possible effect of bilirubin on the distribution and elimination of pentobarbital. The volume of pentobarbital plasma distribution, however, was approximately equal in heterozygous and homozygous data, suggesting no competition between bilirubin and pentobarbital for serum protein.