Suppressive effects of the antiandrogen agent, chlormadinone acetate and the 5alpha-reductase inhibitor, dutasteride on prostate weight and intraprostatic androgen levels in rats.

The objectives of this study were to investigate whether chlormadinone acetate (CMA, Prostal, CAS 302-22-7) more markedly decreased ventral prostate and seminal vesicle weights and exerted more beneficial effects on intraprostatic androgen levels than dutasteride (DUT, CAS 164656-23-9) in rats. Dose-dependent inhibiting effects on prostate and seminal vesicle enlargement were observed after the 14-day administration of CMA (30, 100 mg/kg/day) and DUT (0.3, 1 mg/kg/day). The prostate atrophy rates calculated as the percentages relative to the vehicle-treated group were 50.5 and 67.9% with 30 and 100 mg/kg CMA and 34.9 and 37.0% with 0.3 and 1 mg/kg DUT, respectively, and the atrophying effect of CMA was significantly greater than that of DUT (p < 0.05). The results of 7-day administration were similar to those of 14-day administration. While CMA dose-dependently and significantly (p < 0.05) reduced the testosterone (T) and dihydrotestosterone (DHT) concentrations in prostate, DUT reduced the DHT concentration but markedly increased the T concentration (20-40 times). Even though it was carried out in rats, this study revealed for the first time that the antiandrogen CMA showed a stronger atrophying effect than the 5alpha-reductase inhibitor DUT on direct comparison. The difference between the atrophying effects of CMA and DUT is considered to be attributed to the present results that CMA reduced the concentrations of both androgens (T and DHT) in prostate but DUT did not, and the fact that CMA has a potent androgen receptor-blocking action but DUT does not.

Local injection of a sustained-release antiandrogen formulation into a target prostatic site: an experimental study.

OBJECTIVE: To evaluate the efficacy of one intraprostatic injection with sustained-release chlormadinone acetate (CMA-SR) in rats. MATERIALS AND METHODS: CMA, a steroidal antiandrogen, was enclosed in microcapsules for sustained-release (CMA-SR). Forty-eight rats were divided into group A (intraprostatic CMA-SR 8 mg/kg, one injection), group B (as A but with 25 mg/kg), group C (intraprostatic, vehicle only) and group D (subcutaneous, s.c., CMA 10 mg/kg once daily for 4 weeks). Prostate weight, body weight and plasma testosterone levels were measured for up to 4 weeks. RESULTS: After a s.c. injection with CMA-SR, residual CMA at the s.c. injection site decreased with time. The injected prostate lobe weighed significantly (P < 0.05) less than the contralateral lobe in groups A and B, and significantly (P < 0.05) less in groups A and B than in group C. Both prostate lobes in group D were significantly (P < 0.05) smaller than in group C (P < 0.05). Plasma testosterone levels were significantly lower in group D than in group C (P < 0.05). CONCLUSIONS: The sustained release of CMA after one intraprostatic injection persistently decreased the weight of the target prostate. This new concept of antiandrogen therapy might therefore be effective in man, with fewer systemic adverse reactions.