口服硫酸安普霉素在猪体内的药代动力学和生物利用度研究

Pharmacokinetics and bioavailability of Apramycin sulfate by oral administration in pigs

对 5头健康猪口服和静脉注射国产硫酸安普霉素 ,研究其在猪体内的药代动力学和生物利用度。用微生物法测定血清药物浓度 ,结果平均回收率为 99.0 3%,血清最低检测浓度为 0 .0 5 μg/ ml,日内日间变异系数为 2 .2 %～ 5 .0 %,且血清浓度在0 .0 5～ 3μg/ m l范围呈良好线性关系 (r=0 .996 5 )。以 2 0 mg/ kg口服和以 2 0 mg/ kg静脉注射硫酸安普霉素后 ,经 Mcpkp药代动力学计算机程序处理 ,体内药物运转分别符合开放型一室和二室模型 ,生物半衰期 t1 / 2 分别为 (7.36± 1 .5 2 ) h和 (3.1 7± 0 .75 )h;CLB分别为 4 .82 L / kg· h和 0 .1 6 L / kg· h;AUC值分别为 4 .1 4和 1 30 .6 2。口服 :Cmax为 (0 .2 4± 0 .0 3)μg/ ml;Tp为 (5 .1 2±0 .6 1 ) h;T1 / 2 K为 (7.36± 1 .5 2 ) ;生物利用度 (AUCp.0 / AUCi.v)为 (3.1 92 8± 0 .70 4 4 ) %。

To study pharmacokinetics and availability of national-producing apramycin sulfate by oral and intraveinous administration in 5 pigs.Serum drug concentration was determined with microbiological method,with result that average recovery was 99.03%,the lowest detectable concentration was 0.05 μg/ml in serum,the relative standard deviation (RSD) of intra-day and inter-day assays was (2.2%～)5.0%,within 0.05～3 μg/ml range had a good linear relationship(R=0.9965).While normal pigs were given national-producing apramycin sulfate 20 mg/kg via a single p.o and i.v. adminstration,serum drug concentration-time courses was found to be fitted to a one compartment open model and two compartment open model respectively after dealed with a MCPKP procedure software.The two routes of adminstration's t_(1/2) were 7.36±1.52 h and 3.17±0.75 h respectively;CL_B were 4.83 L/kg·h and 0.16 L/kg·h respectively;AUC were 4.14 and 130.62 respectively.The p.o:C_(max) was(0.24±0.03) μg/ml;Tp was 5.12±0.61 h;T_(1/2K) was 7.36±1.52;the availability(AUCp.o/AUCi.v) was (3.1928±0.7044)%.The results of pharmacokinetics have provided a available theoretical evidence for clinical application.