Abstract: AIM: To investigate the effect of concurrent probenecid administration with different dosages on pharmacokinetics of cefaclor in rats. METHODS: Cefaclor (100 mg·kg^-1, ig) was given alone or in the presence of probenecid (300, 600 and 900 mg·kg^-1, ig) to rats.Serial blood samples were drawn according to the exact time schedule and concentrations of cefaclor were determined by HPLC method. RESULTS: Under the dosages of probenecid ranged from 300 to 600 mg·kg^-1, Cmax and AUC of cefaclor increased, while Vd/F and Cl/F of cefaclor decreased.However, when a still higher dosage (900 mg·kg^-1) of probenecid was used, Cmax of cefaclor decreased, while AUC, Vd F and Cl/F maintained at the levels of those with probenecid 600 mg·kg^-1. CONCLUSION: Probenecid can markedly alter pharmacokinetics of cefaclor and the influential magnitude for each parameter is dependent on the dose of probenecid used in the trial.The Cmax of cefaclor increases with proper dosage of probenecid, while decreases with over dose of probenecid, and this phenomenon may be related to the inhibition of cefaclor intestinal absorption attained with over dose of probenecid.

Key words: cefaclor, probenecid, pharmacokinetics, HPLC