Metabolism of 14C-antipyrine in suspensions of isolated rat liver cells.

Suspensions of liver cells isolated from perfused rat livers were incubated with antipyrine-N-methyl-14C. Antipyrine was eliminated by first-order kinetics during incubations for 3 hours 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 sulphate 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 antipyrine metabolism in primary suspensions by phenylbutazone (1.6 X 10(-3)M), dexamethasone (2 X 10(-4)M) and ethanol (1.3 X 10(-2)M, 0.75%). We suggest that the use of primary suspensions of isolated rat liver cells provide a rapid and simple method for the study of factors influencing drug metabolism in the liver.