阿洛西林在狗的药物动力学参数的反相高效液相色谱法测定

本文用反相高效液相法测定犬静注和肌注阿洛西林20mg/kg后的血中药物浓度,并据此计算有关药物动力学参数。ODS-C_(18)为固定相,甲醇/67mmol/L磷酸缓冲液(1:1,vol/vo1)为流动相,紫外(uv)检测。以对硝基丙酰苯胺为内标物对血清中阿洛西林进行定量测定。根据F值,r 2/1值和AIC(Akaike's Information Criterion)值判断静注和肌注药物后在体内的转运过程分别符合开放型二室和一室模型。静注后即刻血药浓度为218±13μg/mL,T_(1/2α)为0.13h。肌注后T_(max)和T_(1/2ka)分别为0.75和0.24h,C_(max)为16±6μg/mL,但im后AUC仅为iv相同剂量后的38％。该药iv和im后的T_(1/2)分别为1.5和1.7h,V_d分别为0.35和0.43L/kg。本实验结果与微生物法测定结果间无显著差异。

Determination of pharmacokinetic parameters on azlocillin by reverse-phase HPLC method in dogs

Azlocillin is a new semisynthetic ureido-penicillin. In this study, we used the reverse-phase HPLC method to determine the serum concentration of azlocillin in dogs after a bolus iv or im and calculated their phar-macokinetic parameters. The chromatographic column was ODS-C18, and the mobile phase consisted of methanol and PBS (1:1, vol/vol). UV detector was operated at the wave length of 220 nm. p-nitropropionanilide was used as the internal standard to determine the azlocillin concentration in serum. The compartment model was determined by F value, r and AIC. The serum drug concentration-time profile conformed to the two-compartment open model for iv and the one-compartment open model for im injection. After iv injection, the mean peak level was 218± 13 μu,g/mL.r = 0.13h, suggested that the drug was distributed rapidly in the body and reached the effective bactericidal concentration. After im injection, the rmax and T^ke were 0.75 and 0.24 h, respectively. Cmax was 16+6 μg/mL. The bioavailability for the im injection was quite low, as the AUC for im administration was 38% of that for iv administration. The T were 1.5h for iv and T 1.7h for im injection, These results suggested that azlocillin was mainly distributed in the extracellular space and the drug metabolism conformed to the first order kinetics.