Disposition kinetics of barbital in hamsters with hereditary heart failure

Abstract

Within a few minutes after oral administration of sodium barbital, 100 mg/kg, in hamsters with hereditary heart failure, the concentration of the drug was found to be lower in the plasma, kidney, brain and striated muscle of these animals than in the tissue of control hamsters. This could be explained by delayed intestinal absorption, as evidenced by greater amounts of drug recovered from the intestine of cardiomyopathic animals a few minutes after barbital administration. However, 6-24 hours later, the concentration of the drug in these tissues was higher than in those of control hamsters; also, the elimination rate of the drug from these tissues was found to be slower than in control animals. This slower elimination rate of the drug from the tissue of animals in heart failure was responsible for the greater drug bioavailability in the tissues, as reflected by the area under the curve of drug concentration in the tissue vs, time. From in vitro studies of aniline and aminopyrine metabolism by liver microsomal enzymes of hamsters in heart failure, it is concluded that impairment of drug metabolism by the liver may be partially responsible for the slower drug elimination from the body of patients in heart failure.