Creaven P J, Pendyala L, Tremblay D
Department of Medicine, Roswell Park Memorial Institute, Buffalo, New York.
Urology. 1991;37(2 Suppl):13-9. doi: 10.1016/0090-4295(91)80096-p.
Data are available on the pharmacokinetics and metabolism of nilutamide in the rat, dog, and human (normal volunteers and patients with advanced prostatic carcinoma). Studies using 14Carbon-nilutamide, radioimmunoassay, and high-performance liquid chromatography (HPLC) are reviewed. In the rat, bioavailability by the oral route was complete. The majority of the plasma radioactivity was unchanged nilutamide up to six hours, t1/2 was seven hours, and clearance was 150 mL/hour/kg body weight. Metabolism studies identified 6 urinary metabolites. The major metabolites result from reduction of the nitro group initially to an hydroxylamine (17%) and then to a primary amino (26%) group. In normal volunteers the compound was rapidly absorbed, displayed linear kinetics over a dose range of 100-300 mg, and declined slowly in plasma with a terminal phase t1/2 of forty-three to forty-nine hours. In studies in 12 patients with advanced (Stage D) prostatic carcinoma, single-dose kinetics after 14C-nilutamide and kinetics with repetitive twice-daily dosing of two to seven weeks were measured. Terminal phase plasma t1/2 of unchanged nilutamide was 56 +/- 19 hours and of total radioactivity 87 +/- 27 hours (mean +/- SD). Area under the curve of plasma radioactivity was 23 to 38 percent unchanged nilutamide. Urinary excretion of radioactivity was slow and incomplete because the collection time was not long enough in regard to t1/2 (mean after 5 days, 62 +/- 10%) and consisted almost entirely of metabolites. Steady-state plasma levels of nilutamide were reached in about two weeks. It can be concluded that in humans, unlike other species, plasma decay of nilutamide is very slow. Elimination is almost exclusively by metabolism. Single-daily dosing is appropriate. Hepatic impairment could be expected to prolong plasma decay; renal impairment is likely to have little effect.
已有关于尼鲁米特在大鼠、犬和人体（正常志愿者和晚期前列腺癌患者）体内的药代动力学及代谢的数据。本文综述了使用14碳 - 尼鲁米特、放射免疫测定法和高效液相色谱法（HPLC）的研究。在大鼠中，口服途径的生物利用度是完全的。在长达6小时内，血浆中的大部分放射性是未变化的尼鲁米特，半衰期为7小时，清除率为150毫升/小时/千克体重。代谢研究鉴定出6种尿液代谢物。主要代谢物是由硝基最初还原为羟胺（17%），然后再还原为伯氨基（26%）产生的。在正常志愿者中，该化合物吸收迅速，在100 - 300毫克的剂量范围内呈现线性动力学，并且在血浆中缓慢下降，终末相半衰期为43至49小时。在12例晚期（D期）前列腺癌患者的研究中，测定了14碳 - 尼鲁米特后的单剂量动力学以及每日两次重复给药两至七周后的动力学。未变化的尼鲁米特的终末相血浆半衰期为56±19小时，总放射性的半衰期为87±27小时（平均值±标准差）。血浆放射性曲线下面积中未变化的尼鲁米特占23%至38%。放射性的尿液排泄缓慢且不完全，因为就半衰期而言收集时间不够长（5天后平均值为62±10%），并且几乎完全由代谢物组成。尼鲁米特的稳态血浆水平在约两周内达到。可以得出结论，在人类中，与其他物种不同，尼鲁米特的血浆衰减非常缓慢。消除几乎完全通过代谢进行。每日一次给药是合适的。预计肝功能损害会延长血浆衰减；肾功能损害可能影响很小。
