ABSORPTION, METABOLISM AND EXCRETION OF ¹⁴C-GRISEOFULVIN IN MAN

¹ Department of Biochemistry and Department of Physical and Analytical Chemical Research, Schering Corporation, Bloomfield, New Jersey

The absorption, metabolism and excretion of ¹⁴C-griseofulvin (472 mg) after oral administration were studied in man. The metabolic pattern was analyzed in plasma and urine, with and without hydrolysis with Glusulase. Both the total radioactivity and the concentration of griseofulvin in plasma peaked at four hours after drug administration, with levels for total radioactivity and griseofulvin of 2.4 and 1.0 µg/ml, respectively. The half-life for both ¹⁴C-griseofulvin and total radioactivity in plasma was about 22 hours. At four hours after administration, ¹⁴C-griseofulvin accounted for 42% of the total radioactivity in plasma; 6-desmethylgriseofulvin accounted for 44% and other metabolites comprised the remaining 14%. About 50% of the dose was excreted in the urine and 36% in the feces in five days. Using the technique of gas-liquid chromatography and mass spectrometry, we positively identified the major metabolite in urine as 6-desmethylgriseofulvin; its free form represented 47% of the total radioactivity in urine and the glucuronide conjugate represented 37%. A small amount of griseofulvin (0.1% of the dose), 4-desmethylgriseofulvin and several minor, unidentified metabolites were also detected in the urine.