不同剂量丙磺舒对头孢克罗药物动力学的影响

Influence of probenecid on pharmacokinetics of cefaclor

目的 :观察不同剂量丙磺舒 (Pro)对头孢克罗 (Cef)药动学的影响 ,为两者联用提供依据。方法 :家兔 30只随机分成 5组 ;Cef 5 0mg·kg- 1组 ,Cef5 0mg·kg- 1+Pro 5 0mg·kg- 1组 ,Cef 5 0mg·kg- 1+Pro 10 0mg·kg- 1组 ,Cef 5 0mg·kg- 1+Pro2 0 0mg·kg- 1组 ,Cef 2 5mg·kg- 1+Pro 10 0mg·kg- 1组。灌胃给药后于不同时间股静脉取血 ,HPLC法测定Cef血药浓度 ,NDST程序计算药动学参数。结果 :在给予Cef 5 0mg·kg- 1条件下 ,随Pro联用剂量的增大 ,Cef的Cmax、AUC增高而Cl/F、V/F减少 ;Cef2 5mg·kg- 1+Pro 10 0mg·kg- 1组各参数 (除Cl/F外 )与Cef 5 0mg·kg- 1组差异不显著。结论 :Pro可明显改变Cef的药动学 ,在实验剂量范围内其影响程度与丙磺舒剂量有关。Cef 2 5mg·kg- 1联用Pro10 0mg·kg- 1可产生Cef 5 0mg·kg- 1的血药水平。

AIM: To observe the effects of proben-ecid of different doses on pharmacokinetics of cefaclor and to provide the basis of their co-adiministration. METHODS: 30 rabbits were randomly divided into 5 groups: Cef 50 mg·kg -1, Cef 50 mg·kg -1+Pro 50 mg·kg -1,Cef 50 mg·kg -1+Pro 100 mg·kg -1,Cef 50 mg·kg -1+Pro 200 mg·kg -1,Cef 25 mg·kg -1+Pro 100 mg·kg -1. The blood samples were drawn from thigh vein after IG and the concentrations of cefaclor were determined by HPLC. Pharmacokinetics parameters were calculated by NDST procedure. RESULTS: In groups with Cef 50 mg·kg -1, C max and AUC of cefaclor increased, and Vd/F and Cl/F decreased progressively with the adding probenecid. There was no significant difference between Cef 25 mg+Pro 100 mg and Cef 50 mg·kg -1 in each parameter except Cl/F. CONCLUSION: Probenecid can remarkably alter the pharmacokinetics of cefaclor and the magnitude of the effects of probenecid is dependent on its dose in this trial. Cef 25 mg·kg -1 with Pro 100 mg·kg -1 can reach the same blood concentration as Cef 50 mg·kg -1 alone.