注射用硫酸阿司米星单剂给药在健康人体的药代动力学

Pharmacokinetics of single-dose astromicin sulfate in Chinese healthy volunteers

目的研究注射用硫酸阿司米星(胺基糖苷类抗生素)在中国健康受试者单剂量给药的药代动力学。方法采用随机、三交叉、拉丁方设计,12名受试者随机分为3组,先后静脉滴注3个剂量(150,200,250mg)阿司米星。收集的血、尿样本,用柱前衍生化高效液相色谱-荧光法测定其血药浓度。结果 3个剂量组(150,200,250mg)主要药代动力学参数:Cmax分别为(11.27±2.65),(15.83±3.14),(21.97±3.67)mg·L-1;t1/2β分别为(2.56±0.72),(2.97±1.30),(2.66±1.39)h;AUC0-t分别为(30.92±8.49),(39.58±11.57),(47.31±11.59)mg·h·L-1;AUC0-∞分别为(31.78±8.73),(40.50±11.56),(48.20±11.95)mg·h·L-1;Vc分别为(11.49±2.61),(10.69±1.52),(10.20±1.93)L;CL分别为(5.33±2.03),(5.49±1.51),(5.68±1.35)L·h-1。3种剂量12h原型药物尿中累积排泄百分率分别为(78.75±7.00)%,(78.95±12.57)%,(79.94±10.28)%。结论不同给药剂量的阿司米星主要药代动力学参数呈线性分布特性,药物主要通过肾脏排泄,3个剂量消除过程基本一致。

Objective To evaluate the pharmacokinetics of single dose of astrornicin injection in healthy Chinese volunteers. Methods A randomized, three period cross -over, latin -square design study was conducted. Twelve male volunteers were administrated intravenously 150, 200 and 250 mg of astromicin within 0. 5 h infusion. The concentrations of astromicin in serum and urine were determinated by precolumn derivatization -fluorescence HPLC method. Results The main pharmacokinetic parameters of three dose （150, 200, 250 mg） were as follows： Cmax was （11.27±2.65）, （15.83±3.14） and （21.97±3.67） mg· L-1; t1/2βwas （2. 56 ±0. 72）, （2. 97 ± 1.30） and （2. 66 ± 1.39） h; AUC0-1 was （30. 92 ±8.49）, （39.58 ± 11.57） and （47.31 ± 11. 59） mg · h ·L-1; AUC0-∞ was （31.78±8.73）, （40.50 ±11.56） and （48.20± 11.95） mg · h · L-1; Vc was （11.49±2.61）,（10.69±1.52） and （10.20±1.93） L; CLwas （5.33±2.03）, （5.49±1.51） and （5.68 ± 1.35 ） L· h - 1, respectively. Urinary recovery rates was （ 78.75 ± 7.00）%,（78.95 ± 12.57）% and （79.94 ± 10.28）%, respectively. Conclusion The main pharmaeokinetic parameters of astromicin in diferenent doses were nearly fit linear dynamic feature, and the drug maily excreted through kidney.