Bélanger A, Giasson M, Couture J, Dupont A, Cusan L, Labrie F
MRC Group in Molecular Endocrinology, Le Centre Hospitalier de l'Université Laval, Québec, Canada.
Prostate. 1988;12(1):79-84. doi: 10.1002/pros.2990120110.
The present study describes a method for the measurement of the plasma levels of hydroxy-flutamide (Flu-OH), the biologically active and main circulating metabolite of flutamide. We have observed that two to four hours after oral administration of 250 mg of flutamide to healthy young men, as well as to patients with prostate cancer, the plasma concentration of Flu-OH reaches a peak at approximately 1.7 microM. The plasma concentration of Flu-OH measured at months 6, 12, and 18 of treatment shows a minimal basal level of 3.4 microM with a maximal increase at 6.8 to 8.5 microM at 2 to 4 hours. Since the serum levels of testosterone in these patients are approximately 1 nM, the levels of the active antiandrogen are at a 5000- to 10000-fold excess. However, due to the low affinity of the antiandrogen for the androgen receptor, it is extremely important to maintain this concentration of the antiandrogen in plasma constant.
本研究描述了一种测量羟基氟他胺（Flu-OH）血浆水平的方法，Flu-OH是氟他胺的生物活性和主要循环代谢产物。我们观察到，在健康年轻男性以及前列腺癌患者口服250mg氟他胺后两到四小时，Flu-OH的血浆浓度在大约1.7微摩尔时达到峰值。在治疗的第6、12和18个月测量的Flu-OH血浆浓度显示，基础水平最低为3.4微摩尔，在2至4小时时最大增加至6.8至8.5微摩尔。由于这些患者的血清睾酮水平约为1纳摩尔，活性抗雄激素的水平高出5000至10000倍。然而，由于抗雄激素对雄激素受体的亲和力较低，在血浆中维持这种抗雄激素浓度恒定极为重要。
