Nafenopin (2-methyl-2[p-(1,2,3,4-tetrahydro-1-naphthyl) phenoxy]
propionic acid), a phenolic
ether with hypolipidemic properties, given to rats of both sexes for 3 or 14 days, caused an increase in liver weight, peroxisome (microbody) proliferation and smooth endoplasmic reticulum accumulation in hepatocytes. In females, 3 days of
nafenopin administration elicited a significant reduction of
zoxazolamine paralysis time and an enhancement of its metabolism by the 9,000 g supernatant fraction of the liver. In contrast, treatment of males resulted in a prolongation of
paralysis and a decrease of
zoxazolamine hydroxylation. The serum
cholesterol and
triglyceride levels were not changed by short-term administration of the
hypolipidemic drug to female rats, but there was a lowering of
triglycerides in the males. Given for 14 days,
nafenopin reduced
paralysis time to the same extent in both sexes. The in vitro metabolism of
zoxazolamine was similar to that observed after short-term
nafenopin administration. A significant fall in serum
triglycerides was noted in both females and males. The sex difference in
zoxazolamine metabolism was not dependent on endogenous
testosterone.