title: Effect of probenecid on the distribution and elimination of ciprofloxacin in humans.
abstract: 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.
authors.affiliation: IBMP-Institute for Biomedical and Pharmaceutical Research, Nürnberg-Heroldsberg, Germany.
authors.forename: U
authors.initials: U
authors.lastname: Jaehde
authors.forename: F
authors.initials: F
authors.lastname: Sörgel
authors.forename: A
authors.initials: A
authors.lastname: Reiter
authors.forename: G
authors.initials: G
authors.lastname: Sigl
authors.forename: K G
authors.initials: KG
authors.lastname: Naber
authors.forename: W
authors.initials: W
authors.lastname: Schunack
mesh_terms: D000328:Adult; D000890:Anti-Infective Agents / Q000493:pharmacokinetics*; D001826:Body Fluids / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid; D002939:Ciprofloxacin / Q000378:metabolism / Q000493:pharmacokinetics*; D018592:Cross-Over Studies; D004347:Drug Interactions; D005260:Female; D006207:Half-Life; D006801:Humans; D007262:Infusions, Intravenous; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008297:Male; D011339:Probenecid / Q000494:pharmacology*; D012076:Renal Agents / Q000494:pharmacology*; D014018:Tissue Distribution
chemical_list: D000890:Anti-Infective Agents; D012076:Renal Agents; D002939:Ciprofloxacin; D011339:Probenecid