EFFECT OF PROBENECID ON THE DISTRIBUTION AND ELIMINATION OF CIPROFLOXACIN IN HUMANS

Objective: Probenecid-sensitive anion transport systems may be involve d in distribution and elimination processes of anionic drugs, The aim of this study was to determine the effect of multiple probenecid treat ment on the pharmacokinetic disposition of the zwitterionic fluoroquin olone ciprofloxacin in 12 healthy volunteers. Methods: A single intrav enous dose of 200 mg ciprofloxacin was given with and without multiple oral administration of probenecid in a randomized crossover fashion. Serial plasma, mine, saliva, tear, and sweat samples were drawn and an alyzed for ciprofloxacin and its 2-aminoethylamino-metabolite (MI) by reversed-phase HPLC. Results: Plasma area under the concentration-time curve and elimination half-life of ciprofloxacin were increased (p < 0.05), and urinary recovery and total and renal clearance decreased (p < 0.05) in the presence of probenecid, Nonrenal clearance and volume of distribution did not differ significantly with and without coadmini stration of probenecid. Peak plasma concentration, plasma area under t he concentration-time curve, and elimination half-life of M1 were incr eased (p < 0.05) because of the higher amount of M1 formed and the red uced renal clearance (p < 0.05) of the metabolite. Saliva, tear, and s weat exposure were elevated (p ( 0.05), but the alterations can be att ributed primarily to the different kinetics of ciprofloxacin in plasma . Conclusions: Coadministration of probenecid altered the renal excret ion and hence the plasma concentrations of ciprofloxacin. Metabolite k inetics and distribution into saliva, tears, and sweat were affected a ccordingly, but there was no direct effect of probenecid on these proc esses. This type of drug-drug interaction might be of clinical relevan ce when ciprofloxacin is combined with drugs eliminated by the organic anion transport system in the kidney tubules.