Plasma levels of hydroxy-flutamide in patients with prostatic cancer receiving the combined hormonal therapy: an LHRH agonist and flutamide.

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.