静脉滴注法罗培南的人体药动学

Pharmacokinetics of faropenem by intravenous infusion in Chinese healthy volunteers

目的研究静脉滴注法罗培南在人体内的药动学特征。方法12名健康志愿者分成3组(每组男、女各2名),分别单剂量交叉静脉滴注法罗培南200、400和800 mg(用5%葡萄糖注射液稀释至250 mL,于45 min内静脉滴注完毕),采用高效液相色谱-紫外检测法测定血浆及尿液药物浓度。结果受试者血药浓度-时间数据用3p87软件拟合,符合一级消除的二房室模型。静脉滴注法罗培南200、400和800 mg主要药动学参数如下:ρmax(实测值)分别为(24±s 5)、(45±9)和(91±22)mg·L-1;t1/2α分别为(0.38±0.10)、(0.40±0.10)和(0.45±0.10)h;t1/2β分别为(1.31±0.26)、(1.41±0.27)和(1.48±0.28)h;Vc分别为(5.3±1.3)、(5.3±0.8)和(6.1±1.8)L;CL分别为(7.3±1.6)、(7.3±1.5)和(7.6±2.2)L·h-1;K10分别为(1.4±0.3)、(1.37±0.21)和(1.27±0.18)h-1;AUC0～12(以梯形法计算)分别为(30±7)、(59±12)和(116±29)mg.h·L-1。尿累积排泄率分别为(30±12)%、(30±13)%和(29±13)%。ρmax、AUC0～12和AUC0～∞在各剂量组间有非常显著差异(P<0.01),其他药动学参数组间无显著差异(P>0.05);800 mg剂量组的α1、t1/2α和K12在男、女健康受试者间有显著差异(P<0.05),其他药动学参数无性别间差异(P>0.05)。结论健康志愿者静脉滴注法罗培南200～800 mg后的体内过程呈线性特征。

AIM To investigate the pharmacokinetics of faropenem by intravenous infusion in Chinese healthy volunteers. METHODS Twelve healthy volunteers were divided into 3 groups, 2 male and 2 female for every gruop. They received faropenem at single doses of 200, 400, 800 mg respectively for a cross-over design,which were diluted into 250 mL of 5% glucose injection and infused in 45 minutes. The concentrations of faropenem in plasma and urine at different time were assayed by HPLC-UV method. The pharmacokinetics parameters of faropenem were calculated by program 3p87. RESULTS It was found that the plasma concentration-time curves of faropenem by intravenous infusion were fitted to a two-compartment model. The main pharmacokinetics parameters were as follows： ρmax were （24 ± s 5）, （45 ＋ 9）, and （91± 22） mg.L^-1; t＋α were （0.38 ± 0.10）, （0.40± 0.10）, and （0.45 ± 0.10） h; t＋α were （1.31 ± 0.26）, （1.42 ± 0.27）, and （1.48 ± 0.28） h; Vo were （5.3 ± 1.3）, （5.3 ±0.8）, and （6.1 ± 1.8） L; CL were （7.3 ± 1.6）, （7.3 ± 1.5）, and （7.7±2.2） L-h-l; Kl0were （1.4±0.3）, （1.37± 0.21）, and （1.27±0.18） h-l; AUC0-12were （30 ±7）, （59 ± 12）, and （116± 29） mg.h.L^-1. The amount of cumulative recovery of faropenem in urine within 12 h were （30 ± 12） %, （30 ± 13） %, and （29 ± 13）% after the single dose administration of 200, 400, 800 mg, respectively. Among different dose groups, there were significant difference in Pmax, AUC0-12, and AUC0-12 （P 〈 0.01）, but there was no significant difference in other pharmacokinetics parameters （P 〉 0.05）. There was also no significant difference between male and female volunteers （P 〉 0.05） except α, t＋α and K12 of 800 mg group （P 〈 0.05）. CONCLUSION It suggests that the pharmacokinetics of faropenem by intravenous in the dosage range of 200 - 800 mg in human body nearly fits linear dynamic feature.