Endocrine profile of topterone, a topical antiandrogen, in three species of laboratory animals.

Topterone, 17 alpha-propyltestosterone, was administered parenterally or topically to rats, rabbits or hamsters to determine its endocrine profile. Systemic administration demonstrated that topterone was both antiandrogenic and progestational. Topical application failed to elicit a systemic antiandrogenic response at 1 g/kg/day and only a minimal progestational response was seen at 32 mg/kg/day. No other endocrine activities were detected.

Mechanism of action of 17 alpha-propyltestosterone in inhibiting hamster flank organ development.

Win 17,665 [topterone, (17 beta)-17-hydroxy-17-propylandrost-4-en-3-one] inhibited stimulation of flank organ development of castrated immature male hamsters by both testosterone and dihydrotestosterone, whereas progesterone inhibited the stimulation by only testosterone. Topical application of Win 17,665 on the flank organs of the male hamster did not cause any significant effect on testosterone metabolism of this tissue. In addition, there was no decrease in the lipogenic capacity of the flank organ. The evidence presented indicates that Win 17,665 exerts its antiandrogenic action by binding with the cytosolic androgen receptor(s) in the flank organ thus inhibiting the action of dihydrotestosterone.

Metabolic effects of a new hypolipidemic agent, ciprofibrate.

Ciprofibrate, a new orally effective hypolipidemic agent like clofibrate, suppressed tyloxapol-induced hypercholesterolemia in rats. Ciprofibrate at 10 mg/kg was effective. Clofibrate required a dosage of 180 mg/kg to suppress the tyloxapol effect. Norepinephrine-induced free fatty acid release was inhibited by clofibrate in rats in accordance with earlier findings. Ciprofibrate and lifibrate differed from clofibrate in that, at hypocholesterolemically effective doses, neither inhibited the hormone sensitive lipase in vivo.

Blood levels, tissue distribution and the duration of action in rats of ciprofibrate, a new hypolipidemic agent.

The blood levels, distribution and duration of action of ciprofibrate, an orally active hypolipidemic agent, was investigated in rats. Serum concentrations of 30 micrograms of ciprofibrate/ml are associated with significant reductions in both serum cholesterol and triglycerides in rats on a hyperlipidemic diet. Increasing the plasma concentrations of ciprofibrate to 69 micrograms/ml resulted in only a modest incremental reduction in serum lipids. The distribution of radioactivity from [14C]ciprofibrate within rat tissues was not affected by prior treatment for 14 days with ciprofibrate at either 1.5 or 3.0 mg/kg/day. Varying the dosage regimen of ciprofibrate at 30 mg/kg, with medication at intervals of one, 2 or 3 days resulted in similar peak plasma levels of about 300 micrograms/ml, 4 h after medication. The half-life of ciprofibrate, during the terminal disposition phase, was about 82 h. Levels of serum cholesterol remained suppressed up to 3 days after medication with ciprofibrate was discontinued; triglyceride levels returned to control values more slowly.

The results of animal studies with ciprofibrate, a new orally effective hypolipidemic drug.

Findings are given to show that ciprofibrate, a new orally active phenoxyisobutyrate, is significantly more hypolipidemic than is the reference clofibrate. In hyperlipidemic rats ciprofibrate suppresses the increase in blood lipids 33% at a daily dosage of 0.6--3 mg/kg. The corresponding dosage for clofibrate is 125--460 mg/kg. Based on studies with cholesterol pools pre-labeled with [14C]mevalonate or with cholesterol-labeled pools in ciprofibrate-treated normolipidemic rats, ciprofibrate was shown to inhibit cholesterol biosynthesis. No evidence of the presence of 7- or 24-dehydrocholesterol was obtained in the sera of ciprofibrate-treated rats as shown by gas chromatography examination. The order of hypolipidemic effectiveness of ciprofibrate in hyperlipidemic rats provides a basis for anticipating that ciprofibrate will be hypolipidemic in hyperlipoproteinemic subjects who are considered at high risk of acquiring coronary artery disease.

Suppression of sebaceous gland development in laboratory animals by 17alpha-propyltestosterone.

Topical application of the testosterone derivative 17alpha-propylandrost-4-en-17beta-ol-3-one (Win 17665) caused a dose-related regression of the hamster flank organ and guinea pig supracaudal gland in mature male animals. Histological examination confirmed that this action of Win 17665 was on the size of the hamster sebaceous glands and was reversible on cessation of treatment. Topical application of Win 17665 also counteracted flank organ stimulation by directly applied 5-alpha-dihydrotestosterone and 4-androstene-3,17-dione. Seminal vesicle weight was reduced after the repeated subcutaneous administration of 100 mg/kg of Win 17665 but not after repeated oral administration of 320 mg/kg or topical administration of 1 gm/kg of Win 17665.