氟他胺的主要代谢产物2-羟基氟他胺在正常及CCl_4中毒大鼠的药物动力学<英文>

Pharmacokinetics of 2-hydroxyflutamide, a major metabolite of flutamide, in normal and CCl_4-poisoned rats

目的:研究氟他胺的一个主要活性代谢产物2-羟基氟他胺(HF)在正常及CCl_4中毒大鼠的药物动力学。方法:正常及CCl_4中毒大鼠灌胃HF 25mg·kg^(-1),采用高压液相色谱法测定HF浓度,以氟他胺为内标,色谱柱填料为YWG C18,流动相为甲醇:水=3:2(体积比),检测波长为295nm。结果:与正常大鼠比较,HF在CCl_4中毒大鼠的消除明显受到抑制。K由(0.11±0.05)h^(-1)减小到(0.05±0.01)h^(-1)(P<0.01),T_(1/2)由(6.8±1.9)h延长到(14±4)h(P<O.01),Cl由(0.18±0.06)L·kg^(-1)·h^(-1)下降到(0.12±0.02)L·kg^(-1)·h^(-1)(P<0.05),AUC由(149±47)mg·L^(-1)·h增加到(226±54)mg·L^(-1)·h(P<0.05)。结论:该高压液相色谱法灵敏、准确。在CCl_4中毒大鼠,HF的消除明显受到抑制。

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 ig 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 λ 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.