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Effect of probenecid on the distribution and elimination of ciprofloxacin in humans
Author(s) -
Jaehde Ulrich,
Sörgel Fritz,
Reiter Andreas,
Sigl Gabriele,
Naber Kurt G.,
Schunack Walter
Publication year - 1995
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/0009-9236(95)90173-6
Subject(s) - probenecid , ciprofloxacin , chemistry , pharmacokinetics , metabolite , pharmacology , volume of distribution , urine , active metabolite , distribution (mathematics) , medicine , antibiotics , biochemistry , mathematical analysis , mathematics
Objective Probenecid‐sensitive anion transport systems may be involved in distribution and elimination processes of anionic drugs. The aim of this study was to determine the effect of multiple probenecid treatment on the pharmacokinetic disposition of the zwitterionic fluoroquinolone ciprofloxacin in 12 healthy volunteers. Methods A single intravenous dose of 200 mg ciprofloxacin was given with and without multiple oral administration of probenecid in a randomized crossover fashion. Serial plasma, urine, saliva, tear, and sweat samples were drawn and analyzed for ciprofloxacin and its 2‐aminoethylamino‐metabolite (M1) 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 coadministration of probenecid. Peak plasma concentration, plasma area under the concentration‐time curve, and elimination half‐life of M1 were increased ( p < 0.05) because of the higher amount of M1 formed and the reduced renal clearance ( p < 0.05) of the metabolite. Saliva, tear, and sweat exposure were elevated ( p < 0.05), but the alterations can be attributed primarily to the different kinetics of ciprofloxacin in plasma. Conclusions Coadministration of probenecid altered the renal excretion and hence the plasma concentrations of ciprofloxacin. Metabolite kinetics and distribution into saliva, tears, and sweat were affected accordingly, but there was no direct effect of probenecid on these processes. This type of drug‐drug interaction might be of clinical relevance when ciprofloxacin is combined with drugs eliminated by the organic anion transport system in the kidney tubules. Clinical Pharmacology & Therapeutics (1995) 58 , 532–541; doi: