Pharmacokinetics of 2-hydroxyflutamide, a major metabolite of flutamide, in normal and CCl4-poisoned rats

AIM: To study the pharmacokinetics of 2-hydroxyflutamide (HF), a major acti ve metabolite of flutamide (Flu), in normal and CCl4-poisoned rats. METHODS : Normal and CCl4-poisoned rats were given ig HF 25 mg . kg(-1). HF concent rations of plasma were determined by HPLC with YWG C 18 column, Flu was use d as an internal standard. The mobile phase was composed of methanol:water = 3:2 (vol), and absorbance was measured at lambda 295 nm. RESULTS: HF elim ination was inhibited in CCl4-poisoned rats compared with normal rats. K de creased from (0.11 +/- 0.05) to (0.05 +/- 0.01) h(-1) (P < 0.01), T-1/2 was prolonged from (6.8 +/- 1.9) to (14 +/- 4) h (P < 0.01), CI decreased from (0.18 +/- 0.06) to (0.12 +/- 0.02) L . kg(-1) . h(-1) (P < 0.05), AUC incr eased from (149 +/- 47) to (226 +/- 54) mg . L-1 . h (P <0.05). CONCLUSION: This HPLC assay was sensitive and precise, and the elimination of HF was i nhibited due to CCl4 poisoning.