法罗培南钠多剂量静脉滴注在中国健康人体的药代动力学

摘要

Objective To study the pharmacokinetics of faropenem after multiple intravenous infusion administration in Chinese healthy volunteers.Methods Eleven healthy volunteers received faropenem at multiple dose (600 mg, tid 7 d).The concentrations of faropenem in plasma and urine were assayed bv HPLC - UV method.The pharmacokinetic parameters of faropenem were calculated by 3P87 software.Results It was found that the plasma concentration - time curves of faropenem were fitted to a two- compartment model, and physiological dispositions were assumed by linear kinetics characteristics.The main pharmacokinetic parameters were as follows:obtained from the single dose study , Cmax was (62.54 ± 10.58) μg · mL-1;t1/2αwas (0.39 ±0.12) h;t1/2βwas (1.40 ±0.68) h;AUC0-8 was (67.34 ± 11.80) μg · h · mL-1 ;urinary recovery rate was (26.24 ± 10.48 ) ％.The steady - state pharmacokinetic parameters were as follows: C ss min was ( 0.13 ± 0.05 ) μg · mL- 1; C ss max was (58.13 ±9.93) μg · mL-1;Cav was (7.14 ± 1.00) μg · mL-1;t1/2α was (0.31 ±0.05) h;t1/2β was (1.09 ±0.11) h;AUC ss 0-t was (57.15 ± 8.01 ) μg · h · mL-1; urinary recovery rate was ( 30.21 ±15.94) ％.Conclusion The results of multiple dose study showed that the absorption and elimination rate of faropenem was accelerated compared with single dose.%目的 研究多剂量静脉滴注法罗培南钠(β内酰胺类抗生素)在中国健康人体的药代动力学.方法 11名健康志愿者接受多剂量静脉滴注法罗培南钠(600 mg,tid×7 d),用高效液相色谱-紫外检测法,测定法罗培南的血药浓度、尿药浓度,用3P87软件计算药代动力学参数.结果 血药浓度-时间曲线符合二房室模型,体内过程呈线性动力学特征.主要的药代动力学参数:单剂量给药后,Cmax为(62.54±10.58)μg·mL-1;t1/2α为(0.39±0.12)h;t1/2β为(1.40 ±0.68)h;AUC0-8为(67.34±11.80)μg·h·mL-1;尿药累积排泄率为(26.24±10.48)%.多剂量给药达稳态后,Cssmm为(0.13 ±0.05)μg·mL-1;Cssmax为(58.13±9.93)μg·mL-1;Cav为(7.14 ±1.00)μg·mL-1;t1/2α为(0.31±0.05)h;t1/2β为(1.09±0.11)h;AUCss0-t为(57.15±8.01)μg·h·mL-1;尿药累积排泄率为(30.21±15.94)%.结论 多剂量给药后,法罗培南在体内的分布和消除速度较单剂量给药有所加快.