Effects of probenecid on intestinal absorption of cefaclor in rats

Abstract

Abstract: AIM: To investigate the effect of probenecid 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 cefaclor were determined by HPLC and the corresponding parameters were calculated with DAS software.Intestinal absorption experiment:cefaclor (30μg/mL) was co-administered with different dosages of probenecid (0, 90, 180 and 270μg/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 increasing.AUC of cefaclor was positively correlated with probenecid dosage(r=0.997).In contrast, Cl, Vd and V1 of cefaclor were negatively correlated with probenecid dosage(r=-0.837,-0.817 and-0.888, respectively).Meanwhile, the mean residual percentage of cefaclor in perfusate increased dramatically only when probenecid dosage increased to 270μg/mL.CONCLUSION: Proper dosage of probenecid co-administration may result in a decrease in Vd and Cl of cefaclor and an increase in plasma cefaclor concentration. While high dosage of probenecid may decrease the cefaclor plasma concentration.The mechanism underlying may be related to the hindrance effect on cefaclor intestinal absorption with high dosage of pobenecid co-administration, mechanism in detail remains to be clarified.

Key words: probenecid, cefaclor, pharmacokinetics, absorption, HPLC

CLC Number:

R969.1

ZHANG Xiu-hong, MA Zhang-qing, GUI Chang-qing, SONG Jian-guo. Effects of probenecid on intestinal absorption of cefaclor in rats[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2008, 13(12): 1344-1349.

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