注射用头孢曲松钠-他唑巴坦钠人体药代动力学

Pharmacokinetics of ceftriaxone sodium-tazobactam sodium for injection in healthy Chinese volunteers

采用交叉试验设计,研究12名健康受试者分别静脉滴注注射用头孢曲松钠-他唑巴坦钠(4∶1,1.0 g)或注射用头孢曲松钠(0.8 g)的药代动力学特征,确定头孢曲松钠-他唑巴坦钠复方用药是否有药代动力学相互作用。采用HPLC-UV法分别测定血浆中头孢曲松和他唑巴坦的浓度,DAS 2.0软件计算药代动力学参数。受试者分别给予复方制剂和单方制剂后,头孢曲松的主要药代动力学参数分别为:cmax(145.3±14.0)和(123.8±17.1)μg/mL,tmax(0.52±0.04)和(0.51±0.09)h,t1/2(9.02±1.04)和(8.93±0.72)h,MRT0-τ(9.34±0.50)和(9.58±0.42)h,AUC0-τ(979±90)和(984±83)μg.h/mL。给予复方制剂后他唑巴坦相应的药代动力学参数则分别为:(10.4±1.8)μg/mL,(0.53±0.04)h,(1.20±1.66)h,(0.94±0.20)h和(8.33±2.23)μg.h/mL。药代动力学参数统计分析表明,头孢曲松与他唑巴坦无明显的药代动力学相互作用。

Twelve healthy Chinese volunteers（6 men and 6 women） were administered intravenously with ceftriaxone sodium-tazobactam sodium（4 ∶ 1,1.0 g） for injection or ceftriaxone sodium（0.8 g） for injection by a cross-over study design to study the pharmacokinetics of ceftriaxone and tazobactam and to evaluate wheth-er there were pharmacokinetic drug-drug interactions in the compound preparation.The plasma concentrations of ceftriaxone and tazobactam were measured by fully validated HPLC methods,separately.The pharmacokinetic parameters were calculated by DAS 2.0 software.The major pharmacokinetic parameters of ceftriaxone for the compound and single preparations for injection were as follows： cmax（145.3 ± 14.0） and（123.8 ± 17.1） μg/ mL,tmax（0.52 ± 0.04） and（0.51 ± 0.09） h,t1/2（9.02 ± 1.04） and（8.93 ± 0.72） h,MRT0-τ（9.34 ± 0.50）and（9.58 ± 0.42） h,AUC0-τ（979 ± 90） and（984 ± 83） μg.h/mL.Those for tazobactam in the compound preparation for injection were（10.4 ± 1.8） μg/mL,（0.53 ± 0.04） h,（1.20 ± 1.66） h,（0.94 ± 0.20） h and（8.33 ±2.23） mg μg.h/mL,respectively.No significant drug-drug interactions found between ceftriaxone and tazobactam by ANOVA of the pharmacokinetic parameters.