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

C J Xu, D Li
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Abstract

Aim: 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).

Conclusion: This HPLC assay was sensitive and precise, and the elimination of HF was inhibited due to CCl4 poisoning.

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氟他胺的主要代谢物- 2-羟基氟他胺在正常和ccl4中毒大鼠体内的药代动力学
目的:研究氟他胺(Flu)主要活性代谢物2-羟基氟他胺(HF)在正常大鼠和ccl4中毒大鼠体内的药动学。方法:正常大鼠和ccl4中毒大鼠ig HF 25 mg.kg-1。采用高效液相色谱法测定血浆HF浓度,色谱柱为YWG c18,内标为Flu。流动相为甲醇:水= 3:2(体积),在λ 295 nm处测定吸光度。结果:与正常大鼠相比,ccl4中毒大鼠HF消除受到抑制。K从(0.11 +/- 0.05)降低到(0.05 +/- 0.01)h-1 (P < 0.01), T1/2从(6.8 +/- 1.9)延长到(14 +/- 4)h (P < 0.01), Cl从(0.18 +/- 0.06)降低到(0.12 +/- 0.02)l .kg-1 -1 (P < 0.05), AUC从(149 +/- 47)增加到(226 +/- 54)mg. l -1 (P < 0.05)。结论:该方法灵敏、准确,氯化亚铁中毒抑制了HF的清除。
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