复方盐酸头孢噻呋混悬剂的药代动力学研究

Pharmacokinetic Study of Compound Ceftiofur Hydrochloride Suspension

关键词:  头孢噻呋 鱼腥草 药代动力学

Key words:  Ceftiofur  Heartleaf Houttuynia Herb  pharmacokinetic

摘要:

利用药物动力学的方法考察复方盐酸头孢噻呋混悬剂是否具备缓释长效的特点，同时研究鱼腥草油对头孢噻呋药代动力学的影响。36只SPF大鼠随机平均分成三组：A组单剂量注射复方盐酸头孢噻呋混悬剂，B组单剂量注射盐酸头孢噻呋混悬剂，C组单剂量注射头孢噻呋钠粉针；三组注射剂量均为50 mg/(kg?bw)。采用反相高效液相色谱内标法测定血浆药物浓度，并以DAS2.0药动学程序和SPSS（11.0）统计软件对所得数据进行分析。A、B、C组药时数据均符合一级吸收二室模型（权重＝1/cc），主要动力学参数如下：A组：T_1/2Ka=(1.253?0.100)h, T_peak=(2.000?0.000)h，C_max=(35.203?5.732)mg/L，AUC=(229.51?18.278)mg?h/L；B组：T_1/2Ka=(0.341?0.090)h,T_peak=(1.000?0.000)h，C_max=(43.919?1.51)mg/L，AUC=(188.488?9.611)mg?h/L;C组：T_1/2Ka=(0.044?0.012)h,T_peak=(0.167?0.000)h，C_max=(159.091?19.971)mg/L，AUC=(128.554?6.625)mg?h/L。实验数据表明，复方盐酸头孢噻呋混悬剂肌肉注射后，其药物动力学特征表现为吸收缓慢，血药浓度平稳，消除半衰期延长，生物利用度高等特点，在临床上注射1次，连用3 d，可以维持有效血液浓度。

Abstract:

The delayed release characteristic of compound ceftiofur hydrochloride suspension was inspected based on pharmacokinetics, and the impact of Heartleaf Houttuynia Herb on pharmacokinetics was also studied. Thirty-six SPF rat were divided into 3 groups trabant equally. Group A was given compound ceftiofur hydrochloride suspension, group B was given ceftiofur hydrochloride suspension , group C was given ceftiofur sodium. The single injection dose were all 50 mg/(kg?bw). The ceftiofur concentrations in plasma were determined by reversed-phase HPLC. The pharmacokinetic variables were calculated by DAS2.0 PK program and SPSS(11.0) program. The model of group A, B and C all fit a two-compartment model with 1st order absorption(weight= 1/cc). The main pharmacokinetics parameters were as follows: Group A: T1/2Ka=(1.253?0.100)h, Tpeak=2.000?0.000)h，Cmax=(35.203?5.732)mg/L，AUC=(229.51?18.278)mg?h/L；GroupB: T1/2Ka=(0.341?0.090)h, Tpeak=(1.000?0.000)h，Cmax=(43.919?1.51)mg/L，AUC=(188.488?9.611)mg?h/L; Group C: T1/2Ka=(0.044?0.012)h, Tpeak=(0.167?0.000)h, Cmax=(159.091?19.971)mg/L, AUC=(128.554?6.625)mg?h/L. The compound ceftiofur hydrochloride suspension was more slowly absorbed in plasma, decreased the speed of absorption, but enhanced the degree of absorption, retarded the speed of elimination, increased the time of drug action; increased the bioavailability of ceftiofur. It suggested that the dose of compound ceftiofur hydrochloride suspension was once daily by intramuscular injection for 3 to 5 d, and it can keep utility haemoconcentration.