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目的:研究不同剂量丙磺舒联用对头孢克罗肠道吸收的影响及其可能机制.方法:(1)药代动力学试验:头孢克罗(100 mg/kg)对大鼠静脉给药,分别与不同剂量丙磺舒(0、300、600、900 mg/kg)联用,HPLC监测用药后不同时间的血药浓度,DAS软件计算头孢克罗的药代动力学参数.(2)肠道吸收试验:头孢克罗(30μg/Ml)分别与不同剂量丙磺舒(0、90、180、270 μg/Ml)联用,对大鼠在体肠回流给药,给药后不同时间采样,HPLC测定灌流液中头孢克罗浓度的经时变化.结果:(1)头孢克罗静脉给药的血药浓度-时间曲线呈二室开放模型;在试验剂量范围内,随丙磺舒联用剂量增大,头孢克罗的血药浓度呈剂量依赖性增高;AUC与丙磺舒联用剂量呈正相关(r=0.997),而Cl、Vd及V1与丙磺舒联用剂量呈负相关(r=-0.837,-0.817及-0.888).(2)大鼠在体肠回流实验表明,不同剂量丙磺舒联用对头孢克罗肠道吸收影响的程度不同,当丙磺舒联用剂量达270 μg/Ml水平时,灌流液内头孢克罗的留存率明显增高.结论:与适量丙磺舒联用,头孢克罗分布容积及血浆清除率降低,血药浓度增高;而与大剂量丙磺舒联用则明显延缓或抑制头孢克罗的肠吸收,使头孢克罗血药浓度降低,该现象可能与大剂量丙磺舒抑制头孢克罗的肠道吸收有关,其机制有待进一步阐明.“,”AIM: To investigate the effect of pro-benecid on intestinal absorption of cefaclor and possible mechanisms involved. METHODS: Pharmacokinetic experiments: cefaclor (100 mg/kg, I.v. ) was given alone or in the presence of probenecid (300,600 and 900 mg/kg, I. G. ) to rats. Plasma concentrations of ce-faclor were determined by HPLC and the corresponding parameters were calculated with DAS software. Intesti-nal absorption experiment: cefaclor (30 μg/mL) was co-administered with different dosages of probenecid (0,90,180 and 270 μg/mL) using an in vivo perfusion technique in rats. The effect of probenecid on intestinal absorption of cefaclor was investigated by the way of perfusion in the intestine from proximal 2 cm duodenum distal to 10 cm from ligament of Treitz. RESULTS: The plasma cefaclor concentration-time curves after I.v. Administration were fitted to a two-compartment open model. Within the range of experimental dosages, the plasma concentrations of cefaclor increased in a dose-proportional manner with probenecid dosage in-creasing. AUC of cefaclor was positively correlated with probenecid dosage( r =0.997). In contrast, CI, Vd and V1 of cefaclor were negatively correlated with probene-cid dosage(r = - 0.837, - 0.817 and - 0.888, re-spectively). Meanwhile, the mean residual percentage of cefaclor in perfusate increased dramatically only when probenecid dosage increased to 270 μg/mL. CONCLUSION: Proper dosage of probenecid co-ad-ministration may result in a decrease in Vd and CI of cefaclor and an increase in plasma cefaclor concentra-tion. While high dosage of probenecid may decrease the cefaclor plasma concentration. The mechanism un-derlying may be related to the hindrance effect on cefa-clor intestinal absorption with high dosage of pobenecid co-administration, mechanism in detail remains to be clarified.