A comparative study of drug metabolism in the isolated perfused liver and in vivo in rats

The plasma half-lives of five drugs, phenylbutazone, antipyrine, oxotremorine, nortriptyline and desmethylimipramine were compared in vivo and in the isolated perfused rat liver. All drugs showed first order elimination in the perfusion experiments over wide concentration ranges. The half-lives in vivo and in the isolated perfused liver agreed well for drugs with a small volume of distribution (antipyrine, oxotremorine and phenylbutazone) but were markedly different for those with a large volume of distribution (nortriptyline and desmethylimipramine). The half lives of the latter two drugs were 30 times longer in vivo than in the perfused liver. After phenobarbital treatment of rats in vivo the elimination rate of phenylbutazone increased both in vivo and in the isolated perfused liver in a parallel manner. The disappearance of this drug was also shown to be associated with the appearance of its metabolite oxyphenbutazone.