注射用盐酸头孢唑兰在健康人体内的药代动力学研究

目的研究注射用盐酸头孢唑兰在健康人体内的药代动力学。方法 24例健康受试者进行注射用盐酸头孢唑兰单次和多次静脉滴注药动学试验。采用反相高效液相色谱(RP-HPLC)法测定给药后不同时间点头孢唑兰浓度,DAS2.0进行药动学模型拟合和参数计算。结果单次给予低(0.5g)、中(1.0g)、高(2.0g)3个剂量后主要药动学参数:峰浓度Cmax分别为(48.27±9.84)、(77.99±15.08)和(171.59±18.27)mg/L;达峰时间(Tmax)分别为(0.50±0.00)、(0.51±0.23)和(0.51±0.02)h;药-时曲线下面积AUC0-t分别为(92.43±24.02)、(152.45±16.26)和(341.03±44.16)mg.h/L;半衰期(t1/2β)分别为(1.97±0.19)、(2.44±0.24)和(2.18±0.31)h。多次给药(1.0g,2次/d)后主要药动学参数:Cmax为(80.39±11.86)mg/L,Tmax为(0.51±0.02)h,AUC0-t为(159.74±15.06)mg.h/L,t1/2β为(2.55±0.55)h。用药后24h从尿中排出量为(89.4±15.5)%。不同剂量组间Cmax、AUC0-t和AUC0-∞差异均有统计学意义(P<0.05),且与剂量呈线性回归关系(r分别为0.9950、0.9960和0.9963);单、多剂量及男、女受试者间主要药代参数差异均无统计学意义(P>0.05)。结论注射用盐酸头孢唑兰在健康人体内具线性动力学特征,主要药代动力学参数无性别差异,多次给药体内无蓄积作用。

Pharmacokinetics of Injected Cefozopran Hydrochloride in Healthy Volunteers

Objective To study the pharmacokinetics of injected cefozopran hydrochloride in healthy volunteers.Methods 24 healthy volunteers were enrolled to receive low(0.5 g),middle(1.0 g),high(2.0 g) doses of single injection and multiple doses(1.0 g) injection of cefozopran hydrochloride in an open randomized study.The plasma concentrations of cefozopran were determined by RP-HPLC.The DAS2.0 was used to fit the concentration-time data and to calculate the pharmacokinetic parameters.Results The main pharmaeokinetic parameters for a single injection of low,middle and high doses of cefozopran were as follows: Cmax(48.27±9.84),(77.99±15.08) and(171.59±18.27) mg/L;Tmax(0.50±0.00),(0.51±0.02) and(0.51±0.02)h;AUC0-t(92.43±24.02),(152.45±16.26) and(341.03±44.16) mg·h/L;t1/2β(1.97±0.19),(2.44±0.24) and(2.18±0.31) h,respectively.The main pharmacokinetic parameters for a multiple doses injection of cefozopran were as follows: Cmax(80.39±11.86) mg/L;Tmax(0.51±0.02) h;AUC0-t(159.74±15.06) mg·h/L;t1/2β(2.55±0.55) h.The accumulative rate of cefozopran through urine pathway within 24 h was(89.4±15.5)%.The statistical analysis showed that Cmax,AUC0-t and AUC0-∞ increased significantly with increased doses of injection(P<0.05).Those parameters were linearly correlated with the doses of injection(r=0.9950,0.9960,0.9963).However,dosage did not have an impact on other pharmacokinetic parameters(P>0.05).No gender differences in the parameters were found(P>0.05).Conclusion Cefozopran hydrochloride performs a linear kinetics in healthy volunteers.The main pharmacokinetic parameters have no significant gender differences,and there is no drug accumulated with multiple doses of injection.