Prostatic effects induced in dogs by chronic or acute oral administration of 5 alpha-reductase inhibitors

• Published in: The Prostate Vol. 9; no. 1; p. 65
• Main Authors: Brooks, J R, Berman, C, Garnes, D, Giltinan, D, Gordon, L R, Malatesta, P F, Primka, R L, Reynolds, G F, Rasmusson, G H
• Format: Journal Article
• Language: English
• Published: United States 1986
• Subjects: 5-alpha Reductase Inhibitors; Administration, Oral; Animals; Azasteroids - pharmacology; Dihydrotestosterone - analogs & derivatives; Dihydrotestosterone - analysis; Dihydrotestosterone - pharmacology; Dogs; Dose-Response Relationship, Drug; Humans; Male; Prostate - analysis; Prostate - drug effects; Radioimmunoassay; Rats; Testosterone - analysis
• ISSN: 0270-4137
• DOI: 10.1002/pros.2990090110

A series of 4-azasteroidal 5 alpha-reductase inhibitors was tested in dogs to determine the effect of chronic (35-44 day) oral administration on prostate size and histology and acute oral administration on prostatic concentrations of testosterone (T) and dihydrotestosterone (DHT). The extent to which the results of the two tests were correlated was also studied in order to see whether the acute test could be used to predict activity in the chronic test. Six delta 1 analogs of the potent 5 alpha-reductase inhibitor, 4-MA (17 beta-N,N-diethylcarbamoyl-4-aza-4-methyl-5 alpha-androstan-3-one) were uniformly active at low dosage levels (less than or equal to 3 mg/kg) in both types of assay whereas several C1-C2 saturated analogs exhibited little activity in the chronic test. The nature of the side chain and whether there was a methyl or a proton at 4-N did not dramatically influence the activity of delta 1 compounds. There was a broad general agreement between the results of the two kinds of test in that if a compound acutely decreased the prostatic concentration of DHT it was likely to reduce prostate size and alter prostatic histology when given on a chronic basis.