阿苯达唑在人体内的药代动力学研究

PHARMACOKINETICS OF ALBENDAZOLE IN MAN

健康志愿者6人,单剂口服阿苯达唑20mg/kg,用反相高效液相色谱法检测血浆药物浓度。此外监测13例华支睾吸虫病人连续服药6天后的血浆药物浓度。固定相为YWG ODSC_(18)-250×4.6mm,流动相为甲醇-水-冰醋酸(70:30:0.45),紫外检测波长292nm,流速1.0ml,浓度在0.0625-2.0μg/ml之间,药物标准曲线线性关系良好(r=0.9995-0.9998)。单剂口服阿苯达唑20mg/kg后,亚砜及砜的体内过程符合一室模型。其T_(max)分别为4.89h、4.13h;C_(max)分别为0.52μg/ml,0.14μg/ml;T_(1/2Ka)分别为2.14h、1.75h;T_(1/2Ke)分别为6.20h、5.33h。所有标本测定结果,血浆中以亚砜为主,原药及砜的浓度甚低,个体间血药浓度差异较大。

The plasma concentrations of albendazole and its metabolites were determined by a RP- HPLC method in six healthy volunteers after single oral dose (20mg/kg) of ABZ and in patients with clonorchiasis sinensis receiving ABZ consecutively for six days. YWG ODS C_(18) 250×4.6mm was employed as solid phase and methanol-water-acetic acid (70 : 30 : 0.45 .v/ v/v) as mobile phase. Flow rate was 1.0ml/min. UV was at 292nm. The results showe linear in the range of 0. 0625--2.0μg/ml and correlation coefficient for ABZ, ABZ-sulphoxide and ABZ-sulphone were 0. 999.5, 0. 9998, and 0. 9998 respectively. The fate of albendazole-sulphoxide and-sulphone after oral administration confirmed to one compartment model. T_(max) was 4.89h and 4. 13h, C_(max) 0. 52μg/ml and 0.14tμg/ml, T_(1/2Ka) 2. 14h, 1.75h, T_(1/2Ke) 6-20h and 5.33h, respectively. Albendazole-sulphoxide was the major metabolite, while unchanged albendazole and albendazole-sulphone were considerably low. The plasma drug concentrations of individuals varied greatly.