双黄连粉针剂与头孢唑啉钠配伍在家兔体内药动学相互影响

Pharmacokinetic Interaction of Shuanghuanglian Powder for Injection and Cefazolin in Rabbit

目的 研究双黄连粉针剂与头孢唑啉钠配伍在家兔体内药动学相互影响.方法 15只家兔随机分为3组：双黄连粉针剂给药组、头孢唑啉给药组、联合给药组,分别测定不同时间点血药浓度,将血药浓度-时间（p-t）数据以3P97程序（Practical Pharmacokinetic Program-Version 97）拟合,进行房室模型判别及药动学参数计算,并对单独用药组及联合用药组进行比较.结果 双黄连单独用药组与联合用药组中黄芩苷的药-时曲线均符合权重为1/C2的二室开放模型,其主要药动学参数：t1/2α分别为6.66和6.68 min;t1/2β为118.77和48.23 min;Vc为0.086 6和0.108 2 L·kg^-1;AUCo-t为8.98和7.36 kg·min·L^-1,AUC0-∞为9.20和7.47 kg·min·L^-1,MRTo-t为14.19和13.75 min,MRT0-∞为17.91和15.94 min,CLs为0.007 9和0.010 4 L·min^-1·kg^-1.头孢唑啉单独用药组与联合用药组的药-时曲线均符合权重为1/C2的二室模型,其主要药动学参数：t1/2α分别为11.68和14.36 min;t1/2β为46.85和55.59 min;Vc为0.166 9和0.143 9 L·kg^-1;AUC0-t为36.20和56.49 kg·min·L^-1,AUC0-∞为36.51和57.33kg·min·L^-1,MRTo-t为40.28和48.07 min,MRT0-∞为42.55和51.72 min,CLs为0.005 7和0.003 6 L·min^-1·kg^-1.结论 双黄连与头孢唑啉联合用药后,双黄连中黄芩苷药动学参数除Vc显著性升高外,其他参数无显著性变化,而头孢唑啉多项药动学参数发生显著性变化：血药浓度、AUC、MRTo～t显著升高,而CLs显著降低.

OBJECTIVE To study pharmacokinetic interaction of Shuanghuanglian powder for injection and cefazolin in rabbit.METHODS 15 rabbits were divided into three groups randomly. Serum samples were collected at different time after intravenously single dose of Shuanghuanglian, cefazolin or their mixture. The data obtained were fitted with Practical Pharmacokinetic Program-Version 97 （3P97）. RESULTS The mean serum concentrations of baicalin after iv Shuanghuanglian or mixed drugs in rabbits were fitted to a two-compartment model with a weight of 1/C2 .The main pharmacokinetic（PK） parameters of baicalin in two groups were as follows, respectively： t1/2α 6.66 and 6.68 min, t1/2β 118. 77 and 48.23 min, Vc 0.086 6 and 0.108 2 L·kg^-1, AUC0-t 8.98 and 7.36 kg·min·L^-1,AUC0-∞ 9.20 and 7.47 kg·min·L^-1, MRT0-t 14.19 and 13.75 min, MRT0-∞ 17.91 and 15.94 min, CLs 0.007 9 and 0.010 4 L·min·kg^-1 .The mean serum concentrations of cefazolin after iv cefazolin or mixed drugs in rabbits were fitted to a two-compartment model with a weight of 1/C2.The main PK parameters of cefazolin in two groups were as follows,respectively： t1/2α 11.68 and 14.36 min, t1/2β 346.85 and 55.59 min, Vc 0.166 9 and 0.143 9 L·kg^-1, AUC0-t36.20 and 56.49 kg·min·L^-1, AUC0-∞ 36.51 and 57.33 kg·min·L^-1, MRT0-t 40.28 and 48.07 min, MRT0-∞ 42.55 and 51.72 min, CLs 0.005 7 and 0. 003 6 L·min·L^-1· kg^- 1. CONCLUSION There are no significant differences for PK parameters of the baicalin except increasing of Vc after iv mixed drugs. While the PK parameters of cefazolin change largely after iv mixed drugs. The serum concentration, AUC and MRTo_t increase and CL（s） decreases.