A comparative study of griseofulvin- 14c metabolism in the rat and rabbit

Abstract

The excretion and metabolic pathways of griseofulvin- 14C were compared in the rat and rabbit with emphasis on biliary excretion and enterohepatic circulation. It has been shown that, in the rat, griseofulvin metabolism is characterized by extensive biliary excretion and appreciable enterohepatic circulation. In the rabbit, biliary excretion represented a minor pathway and the enterohepatic circulation could not be demonstrated. In the biliary cannulated rat during a 24-hr period, about 77 per cent of the dose (i.v.) was found in the bile and 12 per cent in urine, whereas in the rabbit only 11 per cent was observed in bile and 78 per cent in urine. The major metabolite in rat bile was the 4-demethylgriseofulvin with small amounts of the 6-demethyl derivative present. In rabbit bile, however, the major metabolite was the 6-demethylgriseofulvin with very small amounts of the 4-demethyl derivative present. In addition, small percentages of free griseofulvin and unidentified metabolite(s) were observed in the bile of both species. In urine of the intact and cannulated rats, two major metabolites were present, the 4- and the 6-demethyl derivatives of griseofulvin. Under similar conditions, rabbit urine contained 6-demethylgriseofulvin as the predominant metabolite.