中国健康志愿者单剂静脉滴注甲磺酸帕珠沙星注射液药动学研究

Pharmacokinetics study of pazufloxacin mesylate in single dose in Chinese healthy volunteers

目的研究中国健康成年志愿者单剂静脉滴注甲磺酸帕珠沙星注射液的药动学。方法按GCP指导原则设计试验方案,选择12名18～40岁健康志愿者(男、女各半),按拉丁方设计随机分组,分别依次单剂静脉滴注250、500、750mg3个剂量的甲磺酸帕珠沙星注射液,应用高效液相色谱法(HPLC)测定血药浓度,采用3P97软件进行数据处理,求出药动学参数。结果受试者分别给药后,药-时曲线符合二房室模型,主要药动学参数cmax分别为(4.89±1.11)、(9.94±2.62)、(17.43±3.22)mg/L;t1/2β分别为(1.50±0.19)h、(1.37±0.26)h、(1.53±0.26)h;AUC0～t分别为(9.53±2.00)、(21.47±6.63)、(36.12±3.06)mg·h/L;单剂静脉滴注250、500、750mg甲磺酸帕珠沙星注射液主要经肾排泄,24h经肾累积排泄率分别为(90.19%±10.24)%、(89.36%±9.56)%、(92.97%±3.01)%。结论12名健康受试者分别静脉滴注甲磺酸帕珠沙星注射液后,药-时曲线符合二房室模型,甲磺酸帕珠沙星在250～750mg剂量范围内药物体内过程呈线性动力学特征而无饱和性,主要排泄途径为肾脏。

Objective To investigate the pharmacokinetics of pazufloxacin mesylate of single doses in Chinese healthy volunteers. Methods The protocol was designed according to GCP principle. Twelve volunteers were divided into 3 groups （250mg, 500mg and 750mg） by random Latin square method. The plasma concentrations from the volunteers after injection 250mg, 500mg and 750mg pazufloxacin mesylate were determined by HPLC method and the pharmacokinetcs parameters were calculated by 3P97 software. Results The concentration-time curve matched with two compartment model. The main pharmacokinetics parameters Cmax were （4. 89 ± 1.11） mg/L, （9.94 ± 2.62） mg/L and （ 17.43 ± 3.22） mg/L respectively; t1/2β were （ 1.50 ± 0. 19）h, （ 1.37 ± 0.26） h and （ 1.53 ± 0.26） h respectively ; AUCo-t were （9.53 ± 2.00） mg· h/L, （21.47 ± 6.63） mg·h/L and （36. 12 ± 3.06） mg· h/L respectively; The cumulative excretion rate of pazufloxacin mesylate in urine in 2.4h were （90. 19 ± 10.24）%, （89.36 ±9.56）% and （92.97 ± 3.01 ）% respectively. Conclusion The plasma concentration-time curve fits two compartment model in 12 healthy volunteers after injection pazufloxacin mesylate in single （lose. It suggested that the process of the drug in human body in the dosage range of 250mg - 750mg fit linear dynamic feature and the drug was mainly excreted through kidney.