Neri R
Department of Oncology, Schering Plough Research, Kenilworth, New Jersey.
Urology. 1989 Oct;34(4 Suppl):19-21; discussion 46-56. doi: 10.1016/0090-4295(89)90230-6.
Flutamide is rapidly metabolized by hydroxylation of the side chain to SCH 16423 (alpha, alpha, alpha-trifluoro-2-methyl-4'-nitro-m-lactotoluidide), the major metabolic product in all species studied, which is biologically active in vivo and in vitro studies. Flutamide exhibits its antiandrogenic activity by inhibiting androgen uptake and/or inhibition of nuclear binding of the androgens in the target tissues. At daily doses from 1 to 50 mg/kg body weight, flutamide reduced seminal vesicle and ventral prostate weights of intact male rats without affecting sexual potency. In addition, flutamide reduced the rate of DNA synthesis in the prostate of rats to a greater degree than other steroidal antiandrogens. The antiandrogenic activity was corroborated by the inhibition of androgen-induced prostate hypertrophy in orchiectomized rats through the use of testosterone, testosterone propionate, dihydrotestosterone, androstenedione, and dehydroepiandrosterone. Flutamide, given orally, reduced prostatic size in aged dogs with benign prostate hyperplasia after six weeks and one year. The baboon prostate was also reduced in size when flutamide was administered three times a week for four weeks.
氟他胺通过侧链羟基化迅速代谢为SCH 16423（α，α，α-三氟-2-甲基-4'-硝基间乳酰甲苯胺），这是所有研究物种中的主要代谢产物，在体内和体外研究中均具有生物活性。氟他胺通过抑制雄激素摄取和/或抑制靶组织中雄激素的核结合来发挥其抗雄激素活性。在每天1至50毫克/千克体重的剂量下，氟他胺可降低完整雄性大鼠的精囊和腹侧前列腺重量，而不影响性功能。此外，氟他胺比其他甾体类抗雄激素更能降低大鼠前列腺中的DNA合成速率。通过使用睾酮、丙酸睾酮、二氢睾酮、雄烯二酮和脱氢表雄酮抑制去势大鼠雄激素诱导的前列腺肥大，证实了其抗雄激素活性。口服氟他胺六周和一年后，可使患有良性前列腺增生的老年犬的前列腺体积缩小。当每周三次给予氟他胺，持续四周时，狒狒的前列腺体积也会减小。
