Metabolism of 14C‐Antipyrine in Suspensions of Isolated Rat Liver Cells

Abstract

Suspensions of liver cells isolated from perfused rat livers were incubated with antipyrine-N-methyl-14C. Antipyrine was eliminated by 1st order kinetics during incubations for 3 h with primary suspensions (parenchymal cells + non-parenchymal cells) and suspensions of purified parenchymal cells. Antipyrine concentrations were unchanged when incubated with suspensions of non-parenchymal cells, dead cells or medium only. At the end of incubation period, 4-OH-antipyrine and 3-CH2OH-antipyrine were detected mainly as the glucuronide or sulfate conjugates and evidence for the N-demethylation of antipyrine was also obtained. Half-lives for elimination of antipyrine in primary cell suspensions were not significantly different from the half-lives measured in parenchymal cell suspensions. This finding together with the lack of metabolism of antipyrine found in non-parenchymal cell suspensions suggest that oxidation and conjugation of antipyrine is mainly confined to the parenchymal cells. There was significant inhibition of anitpyrine metabolism in primary suspensions by phenylbutazone (1.6 .times. 10-3 M), dexamethasone (2 .times. 10-4 M) and ethanol (1.3 .times. 10-2 M, 0.75%). The use of primary suspensions of isolated rat liver cells appears to provide a rapid and simple method for the study of factors influencing drug metabolism in the liver.