Brooks J R, Berman C, Garnes D, Giltinan D, Gordon L R, Malatesta P F, Primka R L, Reynolds G F, Rasmusson G H
Prostate. 1986;9(1):65-75. 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.
对一系列4-氮杂甾体5α-还原酶抑制剂在犬类身上进行了测试，以确定长期（35 - 44天）口服给药对前列腺大小和组织学的影响，以及急性口服给药对前列腺中睾酮（T）和双氢睾酮（DHT）浓度的影响。还研究了这两项测试结果的相关程度，以查看急性测试是否可用于预测长期测试中的活性。强效5α-还原酶抑制剂4-MA（17β-N，N-二乙基氨基甲酰基-4-氮杂-4-甲基-5α-雄甾烷-3-酮）的六种δ1类似物在两种类型的试验中，在低剂量水平（小于或等于3 mg/kg）时均具有一致的活性，而几种C1 - C2饱和类似物在长期测试中表现出几乎没有活性。侧链的性质以及4-N处是甲基还是质子，对δ1化合物的活性没有显著影响。两种测试结果之间存在广泛的总体一致性，即如果一种化合物能急性降低前列腺中DHT的浓度，那么在长期给药时它很可能会减小前列腺大小并改变前列腺组织学。
