The metabolism of griseofulvin in mammals

Abstract

Griseofulvin [7chloro-4:6:2'-trimethoxy-6'methylgris-2'-en-3:4'-dione (I:R, R', Me)], a product of Penicillium gri8eofulvum Dierckx, was first isolated by Oxford, Raistrick & Simonart (1939): its structure was first established by Grove, Ismay, MacMillan, Mulholland & Rogers (1951). This compound has fungistatic activity and was reported to control experimental ringworm in guinea pigs (Gentles, 1958) and in calves (Lauder & O'Sullivan, 1958) when administered orally.

High‐Pressure Liquid Chromatographic Assay for Griseofulvin in Plasma

“…The uncorrected melting point of the material isolated from the urine extracts was 280°, in reasonable agreement with the 273-275' melting point reported previously for 6-demethylgriseofulvin (7). The recovery of 87 mgof metabolite after the administration of the 1-g dose is similar to the reported 7% (8) and 10% (2) recoveries 24 hr after administration of a 500-mg dose to a human subject.…”

“…No attempt was made to recover 6-demethylgriseofulvin that might have been present as a glucuronide metabolite in the urine. The UV absorption maxima in alkaline solution were 250 and 300 nm, conipared to previously reported values of 249.5 and 330 nm (7). Similarly, the maxima were 236 and 293.5 nm in acidic solution, compared to 235.5 and 293.5 nm.…”

“…Griseofulvin Metabolite Isolation-6-Demethylgriseofulvin has been reported to be the primary griseofulvin metabolite in humans (6,7). Thus, it is logical to assume that the major source of interference in the fluorometric assay procedures can be attributed to this metaholite.…”

“…The recovery of 87 mgof metabolite after the administration of the 1-g dose is similar to the reported 7% (8) and 10% (2) recoveries 24 hr after administration of a 500-mg dose to a human subject. Similarly, 10.5% of a 1-g dose in a 24-hr urine sample was obtained from a human suhject (7). No attempt was made to recover 6-demethylgriseofulvin that might have been present as a glucuronide metabolite in the urine.…”

Absorption Characteristics of Solid Dispersed and Micronized Griseofulvin in Man

“…No intact griseofulvin was detected. The excretion of the intact griseofulvin was reported to be negligible in man (8,9) and in other animals (8-14). The metabolites were shown to be excreted through the bile after intravenous administration of radioactive gri~eofulvin-~4C to rats and rabbits (14) but not dogs (15).…”