Griseofulvin (7-chloro-4:6:2'-trimethoxy-6'-methylgris—2'-en-3:4'-dione) 
[7-chloro-4, 6-dimethyoxycoumaran-3-one-2-spiro-1'-(2'-methoxy-6'- 
methylcyclohex-2'-en-4'-one) ] 
C13°_Labeled griseofulvin was administered orally to rabbits, rats 
and humans. Examination of urine samples indicated that both 4- and 6- 
demethylgriseofulvin were excreted. These were present as free compounds 
as well as conjugates. In rats, the relative amounts of these two com- 
pounds changed with time, with 4-demethyl analog increasing and the 6- 
demethyl analog decreasing. The latter was excreted primarily in the free 
form while 4-demethylgriseofulvin appeared largely in the conjugated form. 
In vitro studies produced the same metabolites (84, 1380, 1381, 1382). In 
other studies, the metabolite 3-chloro-4,6-dimethoxysalicylic acid was 
Observed in rabbit urine (1417). 
During studies on the enzymatic destruction of griseofulvin by fungi, 
three different monodemethylgriseofulvins were demonstrated. Microsporum 
canis produced 7-chloro-4-hydroxy-6,2'-dimethoxy-6'-methylgris-2'-en-3,4'- 
dione (4-demethylgriseofulvin); Botrytis allii produced griseofulvic acid 
(2'-demethylgriseofulvin); and Cercospora melonis gave rise to 7-chloro-6- 
hydroxy-4,2'-dimethoxy-6'-methylgris-—2'-en-3,4-dione (6-demethylgriseofulvin) 
(141). 
Studies with a pseudomonas gave evidence that griseofulvin was de- 
chlorinated and that ring rupture occurred. No metabolites were identi- 
fied (1523). 
The elucidation of the complex structure of griseofulvin was covered 
in a series of four papers (565, 566, 567, 568). 
Absorption kinetics of griseofulvin in man were studied. The plasma- 
concentration curve was described by a bi-exponential equation; the half- 
life for the first exponent was 0.70 - 1.7 hr. and the second 9.5 - 2.1 hr. 
Absorption occurred up to 30 hours after administration and 27 - 72.5% of 
the dose was absorbed (1635). 
In studies with dogs, 6-demethylgriseofulvin was the primary 
metabolite. This was excreted in the urine in the free form (40-57%) and 
as the glucuronic acid conjugate (25%). Only a small amount of the 6- 
demethyl analog was found in the bile (6%). The plasma disappearance 
curves of griseofulvin in dogs after intravenous injection were 
220 
