Abstract: AIM:To investigate the effects and quantitative relations of co-administering probenecid OF different dosages on pharmacokinetics of cefaclor in rab- bits and approach the possible mechanisms involved as well.METHODS:Monitor plasma and urine cefaclor concentrations .24 male rabbits were randomly divided in- to 4 groups by Cefaclor 50 mg·kg ^-1 , Cefaclor 50 mg·kg ^-1 + Probenecid 100 mg·kg^-1 , Cefaclor 50 mg·kg ^-1 +Probenecid 250 mg·kg ^-1 and Cefaclor 50 mg·kg ^-1 +Probenecid 625 mg·kg ^-1 .Blood and urine samples were collected according to the regular time schedule after intragastric administration .The concentra- tion of cefaclor in blood and urine were determined by HPLC.Pharmacokinetic parameters were calculated by DAS ( Drug and Statistical) software .Measur plasma pro- tein-binding rate of cefaclor .The experimental groups and drug dosage were same as described above.The blood sample was drawn at 1 hour after administration, and the protein-binding rate of cefaclor was determined by equi- librium dialysis .RESULTS:Within the dosages of pro- benecid ranged from 0 -250 mg·kg ^-1 , T_{1/ 2ka}, T_max, C_max and AUC of cefaclor increased in accordance with increas- ing dosage of co-administering probenecid while CL/F and Vd/F were decreased ( P <0 .01) ;However, when the dosage of co-administering probenecid was 625 mg·kg ^-1 , C_max of cefaclor strikingly decreased ( P <0 .01) , while AUC and CL/F maintained at the levels of those with pro- benecid 250 mg·kg ^-1 .In this experiment, urinary excre- tive peak time of cefaclor in its prototype postponed grad- ually, biological half life prolonged and urinary excretive accumulation percentage decreased obviously( P <0 .01) . To the dosages of probenecid ranging from 0 -250 mg·kg ^-1 , protein-binding rate of cefaclor decreased nota- bly( P <0 .01)going with increasing dosages of co-admin- istration probenecid ;While the dosage of co-administra- tion probenecid reached 625 mg·kg ^-1 , the protein-bind- ing rate of cefaclor corresponded to that of cefaclor 50 mg·kg ^-1 without probenecid ( P >0 .05) .CONCLU- SION:Co-administering probenecid can strikingly change pharmacokinetics of cefaclor and the influential degree of pharmacokinetics parameters is dependent on dosages of probenecid used in the experiment .Biological half life prolongs and urinary excretive accumulation percentage of cefaclor decreases obviously .

Key words: probenecid , cefaclor , pharmacokinet- ics , urine drug level , HPLC , equilibrium dialysis , pro- tein-binding rate ofcefaclor