Pharmacokinetics of 2-hydroxyflutamide, a major metabolite of flutamide, in normal and CCl4-poisoned rats.
OBJECTIVE
To study the pharmacokinetics of 2-hydroxyflutamide (HF), a major active metabolite of flutamide (Flu), in normal and CCl4-poisoned rats.


METHODS
Normal and CCl4-poisoned rats were given i.g. HF 25 mg.kg-1. HF concentrations of plasma were determined by HPLC with YWG C 18 column, Flu was used 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 elimination was inhibited in CCl4-poisoned rats compared with normal rats. K decreased from (0.11 +/- 0.05) to (0.05 +/- 0.01) h-1 (P < 0.01), T1/2 was prolonged from (6.8 +/- 1.9) to (14 +/- 4) h (P < 0.01), Cl decreased from (0.18 +/- 0.06) to (0.12 +/- 0.02) L.kg-1.h-1 (P < 0.05), AUC increased from (149 +/- 47) to (226 +/- 54) mg.L-1.h (P < 0.05).


CONCLUSIONS
This HPLC assay was sensitive and precise, and the elimination of HF was inhibited due to CCl4 poisoning.
Xu
C J
CJ
Department of Pharmacology, School of Pharmacy, Shanghai Medical University, China. dli@shmu.edu.cn
Li
D
D
D000726:Androgen Antagonists / Q000493:pharmacokinetics*; D000818:Animals; D002252:Carbon Tetrachloride Poisoning / Q000378:metabolism*; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D005485:Flutamide / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D008297:Male; D051381:Rats
D000726:Androgen Antagonists; C014290:hydroxyflutamide; D005485:Flutamide