注射用比阿培南单剂量及多剂量静脉滴注给药的人体药动学研究

摘要

OBJECTIVE: To investigate the pharmacokinetics of Biapenem for injection with a single and multiple dose administration in Chinese healthy volunteers. METHODS: In single-center open randomized controlled design, 12 healthy volunteers received a single dose intravenous infusion of 300 mg biapenem, and then they were repeatedly administrated with 300 mg biapenem every 12 hour for 5 days. The concentrations of biapenem in plasma and urine were determined by HPLC. DAS pharmacokinetics software was used for data process and calculation of pharmacokinetic parameters. RESULTS: The main pharmacokinetic parameters of biapenem after single dose of 300 mg Biapenem for injection were as follows: cmax ( 13.74 ± 4.40) mg· L- 1; tmax (0.51 ± 0.11 ) h; t1/2β( 1.34 ± 0.41 ) h; t1/2z( 1.18 ± 0.23) h; AUC0～t( 15.60 ± 2.95)mg· h· L-1; the 12 h cumulative urine excretion rate was (33.04 ± 13.54)％. The main pharmacokinetic parameters of biapenem after multiple dose administration were as follows: cssmm couldn't be detected; cssmax(15.12 ±3.27) mg·L-1;cssav(1.43±0.23) mg·L-1;tssmax(0.49±0.05) h; t1/2β(1.33 ±0.39) h; t1/2z(1.02±0.18) h; AUC0～t ( 17.18 ± 2.73) mg· h· L- 1; the fluctuation coefficients of plasma concentration DF was ( 10.56 ± 1.55) ％. CONCLUSION: No accumulation is detected when 300 mg biapenem for injection has been administrated every 12 hour for 5 days, it is safe.%目的:研究注射用比阿培南单剂量及多剂量静脉滴注的人体药动学过程.方法:采用单中心、开放、随机自身对照设计,12名健康受试者单剂量恒速静脉滴注注射用比阿培南300mg;单剂量试验结束后进入多剂量给药试验,q12h,连续给药5 d.采用高效液相色谱法测定血浆和尿液中比阿培南的浓度,并采用DAS药动学软件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注射用比阿培南后,主要药动学参数分别为cmax(13-74±4.40)μg·mL-1,tmax(0.51±0.11)h,t1/2β(1.34±0.41)h,t1/2z(1.18±0.23)h,AUC0～1(15.60±2.95)μg·h·mL-1,12 h平均尿液累积排泄率为(33.04±13.54)%.多剂量静脉滴注达稳态后的主要药动学参数cssmm因低于定量下限而未检测出,cssmax为(15.12±3.27)μg·mL-1,cssav为(1.43±0.23)mg·L-1,tssmax为(0.49±0.05)h,t1/2β为(1.33±0.39)h,t1/2z为(1.02±0.18)h,AUC0～1为(17.18±2.73)μg·h·mL-1,血药浓度波动系数DF为(10.56±1.55)%.结论:注射用比阿培南静脉滴注给药300mg,q12h,连续给药5d,药物在体内无蓄积,安全性好.