注射用法罗培南钠的单剂量和多剂量药代动力学研究

Pharmacokinetics of faropenem sodium after a single or multiple intravenous doses in Chinese healthy volunteers

目的考察单次和连续静脉滴注法罗培南钠注射液后健康人体内的药动学过程。方法12名健康受试者随机交叉单剂量静脉滴注给药100,200,300,600mg,单剂量试验结束后进入多剂量试验,8名受试者静脉滴注给药每次200mg,每日3次,连续给药7d,用高效液相色谱法测定血浆和尿中法罗培南的浓度,并采用药动学程序对试验数据进行处理,求算有关药动学参数。结果12名健康受试者单剂量静脉滴注法罗培南注射液后,主要药动学参数Cmax分别为(8.42±1.96)mg/L,(16.64±3.09)mg/L,(24.73±3.58)mg/L,(44.43±3.93)mg/L,T1/2分别为(1.72±0.72)h,(1.60±0.33)h,(1.56±0.21)h,(1.36±0.09)h,AUC0-t分别为(13.90±2.96)mg.h/L,(26.98±5.75)mg.h/L,(38.29±5.29)mg.h/L,(70.58±10.33)mg.h/L,12h累积尿药排泄率分别为31.4%,31.5%,30.5%,34.9%,多次静脉滴注后的主要药动学参数Cmax,T1/2,AUC0-t分别为(15.83±3.96)mg/L、(1.11±0.27)h、(21.93±3.59)mg.h/L,血药浓度波动系数和Cav分别为(5.34±1.30)和(2.74±0.45)mg/L,12h累积尿药排泄率为40.5%。结论单次给药在100～600mg剂量范围内法罗培南呈线性消除,性别对法罗培南的药代动力学过程无影响,肾脏是法罗培南的主要排泄器官,连续多次给药在体内无蓄积。

Objective The pharmacokinetics of faropenem were studied in single and multiple dose regimens. Methods A single-dose, open-label, randomized, four-period crossover dose study was carried out in 12 healthy volunteers. The subjects received intravenous infusion of 100, 200, 400 or 600 mg faropenem. 8 subjects were given 200mg of faropenem q8h for 7 days. The concentrations of faropenem in serum and urine were determined by HPLC method. Results The main pharmacokinetic parameter of the four groups （100,200,400 and 600 mg） were as follows： Cmax = （8.42 ±1.96） mg/L, （16. 64 ±3.09） rag/L,（24.73 ±3.58） mg/L, （44. 43 ±3.93） mg/L,T1/2 = （1.72 ±0.72） h,（1.60±0.33）h,（1.56±0.21）h,（1.36±0.09）h,AUC0-t= （13.90-±2.96） mg·h/L, （26.98 ±5.75） mg·h/L, （38.29±5.29） mg·h/L, （70.58 ± 10.33） mg·h/L,respeetively. Almost 30% of the administered drug was excreted unchanged in urine up to 12h after dosing. The steady-state pharmacokinetie parameters including C T1/2, AUC0.8, DF and Cav were （ 15.83 ± 3.96） mg/L, （ 1.11 ± 0.27 ） h , （ 21.93 ± 3.59 ） mg· h/L, （ 5.34 ± 1.30 ） and （ 2.74 ± 0.45 ） mg/L, respectively. Conclusion In single-dose study, Cmax and AUC demonstrated linear pharmacokinetics from 100 to 600 mg. The accumulated recovery rates obtained in urine indicate renal excretion is the main pathway for the elimination of faropenem. No significant differences between genders were observed. Moreover, all doses of faropenem were well tolerated. There was no accumulation when faropenem was given with multiple doses.