化合物Au20大鼠体内药动学及绝对生物利用度研究

目的建立HPLC法测定大鼠血浆中化合物Au20的浓度,研究其在大鼠体内的药动学及绝对生物利用度。方法双周期自身交叉设计,SD大鼠静注给药和灌胃给药化合物Au20,剂量分别为4.0和40.0 mg/kg,给药后不同时间点取血,HPLC法测定血浆中化合物Au20的浓度,用DAS 2.0软件计算其药动学参数。结果血浆中化合物Au20在7.8～1 000 ng/mL浓度范围内线性关系良好(r=0.999 9),提取回收率75.91%～89.06%,日内和日间RSD均小于5%。静脉注射给药的药-时曲线符合三室模型。经剂量校正,口服给药的绝对生物利用度为(4.08±1.85)%。结论化合物Au20口服给药的绝对生物利用度低。

Pharmacokinetics and absolute bioavailability of compound Au20 in rats

Objective To establish an high performance liquid chromatography(HPLC) method for determination of compound Au20 concentration in plasma and investigate its pharmacokinetics and absolute bioavailability in rats.Methods Based on the random two-way cross-over design,4.0 and 40.0 mg/kg compound Au20 were given via iv and ig respectively to SD rats.Blood samples were collected at various time points after administration.Plasma concentration of compound Au20 in rats was measured by HPLC.Pharmacokinetic parameters were calculated by DAS 2.0 program.Results The calibration curve was linear in the range of 7.8~1 000 ng/mL(r=0.999 9).The extraction recoveries were 75.91%~89.06%,with the intra-and inter-RSDs less than 5%.The pharmacokinetics behavior of compound Au20 iv could be described by a three-compartment model.The absolute bioavailability of oral administration was(4.08±1.85) % after correction of dosage.Conclusion The compound Au20 shows low absolute bioavailability in rats after oral administration.