法罗培南钠在健康受试者单剂量及多剂量静脉滴注的药代动力学研究  

Pharmacokinetics of faropenem sodium for injection after a single and multiple intravenous dose in healthy volunteers

作　　者：沈金芳[1] 孙黎[1] 苏克剑[1] 刘瑾[1] 

机构地区：[1]上海交通大学医学院附属仁济医院临床药理研究室,上海200001

出　　处：《中国药理学通报》2010年第3期392-396,共5页Chinese Pharmacological Bulletin

基　　金：国家科技部十一五计划"重大新药创制"科技重大专项基金资助项目(No2008ZX09312)

摘　　要：目的研究12名健康志愿者按400mg单剂量和多剂量静脉滴注注射用法罗培南钠后的药代动力学。方法多剂量给药方案为每天2次,连续5次。采用高效液相色谱法测定法罗培南钠的血药浓度及尿药浓度。血药浓度—时间数据用3p87软件处理,按两室模型拟合并求算药代动力学参数。尿药排泄数据采用尿药速率法。结果单剂量给药后的药代动力学参数分别为:Cmax为(45.20±8.73)mg.L-1;T12α为(0.401±0.096)h;T12β为(1.419±0.267)h;AUC0-12(以梯形法计算)分别为(59.216±11.886)mg.h.L-1;尿累积排泄率为(30.48±12.77)%,T12为(0.993±0.088)h,Ke为(0.227±0.097)h-1。多剂量给药达稳态后的药代动力参数分别为:Cmssin为(0.03±0.02)mg·mL-1;Csmsax为(44.60±9.08)mg·mL-1;Cav为(4.939±1.048)mg.L-1;(T_1/2)α为(0.340±0.105)h;(T_1/2)β为(1.257±0.173)h;AUC0ss-τ为(59.268±12.571)mg.h.L-1;尿累积排泄率为(40.55±17.53)%,T_1/2为(1.085±0.069)h,Ke为(0.296±0.136)h-1。结论该药在人体内的分布和消除速度不随连续给药而变化。按400mg,每天2次的给药方案,在体内可达到有效血药浓度,且安全性好,适合临床推广应用。Aim To study the pharmacokinetics of faropenem sodium for injection after a single and multiple intravenous dose in 12 healthy volunteers.Methods Multiple-dose regiments used 12-hour dosing intervals for 5 doses.Plasma and urine faropenem sodium concentrations were measured using high-performance liquid chromatography.The concentration-time curves of faropenem sodium were fitted to a two-compartment open model.The excretion data in urine were disposed by the method of excretion rate in urine.Results The pharmacokinetic parameters obtained from the single-dose study were as follows：Cmax=（45.20±8.73）mg·L-1;T12α=（0.401±0.096）h;T12β=（1.419±0.267）h;AUC0-12=（59.216±11.886）mg·h·L-1.The steady-state pharmacokinetic parameters were：Cssmin=（0.03±0.02）mg·L-1;Cssmax=（44.60±9.08）mg·L-1;Cav=（4.939±1.048）mg·L-1;（T_1/2）α=（0.340±0.105）h;（T_1/2）β=（1.257±0.173）h;AUCss0-12=（59.268±12.571）mg·h·L-1.The amount of cumulative recovery of faropenem sodium in urine for single and multiple dose within 12 h was（30.48±12.77）% and（40.55±17.53）%,respectively.The pharmacokinetic parameters in urine of the single-dose study were：T_1/2=（0.993±0.088）h,Ke=（0.227±0.097）h-1.The steady-state pharmacokinetic parameters in urine were：T_1/2=（1.085±0.069）h,Ke=（0.296±0.136）h-1.Conclusions The distribution and elimination rates of faropenem sodium for injection are not changed after multiple intravenous administrations.Effective concentrations in vivo can be achieved after the repeated administration with 400 mg twice a day regiment.The dosing schedule can be recommended.

关 键 词：注射用法罗培南钠 药代动力学 高效液相色谱法 单剂量 多剂量 人类实验 

分 类 号：R944.11[医药卫生—药剂学] R978.1[医药卫生—药学]