METABOLISM OF GRISEOFULVIN IN DOGS

Quantitative and qualitative aspects of griseofulvin metabolism in the dog are presented. The plasma disappearance curves of griseofulvin in dogs after intravenous injection were biexponential. In two dogs the average half‐lives were 4 and 47 min. for the fast and slow exponential components, respectively. Plasma clearance values were 487 and 588 ml./min. in these two dogs. After intravenous administration a metabolite of griseofulvin in the urine was isolated and confirmed to be 6‐demethylgriseofulvin. Approximately 40 and 57% of the dose was found to be excreted as 6‐demethylgriseofulvin in two dogs given doses of griseofulvin ranging from 100 to 280 mg. An additional 25% of the dose was excreted as 6‐demethylgriseofulvin glucuronide. Biliary excretion of intact griseofulvin was absent and less than 3% of the dose was excreted in the bile as 6‐demethylgriseofulvin. Based on these studies, it appears that the dose of griseofulvin presently used in dogs for dermatomycoses is inadequate. A new dosage calculated to be 90 mg./kg./day is probably required to maintain therapeutically effective body levels of griseofulvin. Copyright © 1969 Wiley‐Liss, Inc., A Wiley Company