title: Target site concentrations of ciprofloxacin after single intravenous and oral doses.
abstract: To characterize the potential of ciprofloxacin penetration into human soft tissues following intravenous (i.v.) and oral (p.o.) administration, we measured the free ciprofloxacin concentrations in interstitial space fluid of skeletal muscle and subcutaneous adipose tissue by microdialysis. In addition, ciprofloxacin concentrations were measured in cantharis-induced skin blisters, saliva, and capillary plasma and were compared to the total concentrations in venous plasma. Furthermore, a pharmacodynamic in vitro model was used to simulate in vivo pharmacokinetics in bacterial culture. Eight healthy volunteers received ciprofloxacin in an open randomized crossover fashion either as a single i.v. infusion of 400 mg over 60 min or as a single p.o. dose of 500 mg. For both tissues the mean areas under the concentration-time curves (AUCs) for interstitial space fluid (AUC(interstitial fluid)s) were significantly lower than the corresponding AUC(plasma)s, with AUC(interstitial fluid)/AUC(plasma) ratios ranging from 0.38 to 0.68. For skeletal muscle, the AUC(interstitial fluid) was significantly higher after administration of 400 mg i.v. than after administration of 500 mg p.o., with a ratio of the AUC after p.o. administration/AUC after i.v. administration of 0.64. The ratio of the concentration in skeletal muscle/concentration in plasma increased over the entire observation period, implying that ciprofloxacin concentrations were not at steady state. The ratio of the concentration in skin blister fluid/concentration in plasma reached values above 4, indicating a preferential penetration of ciprofloxacin into inflamed lesions. The concentrations in saliva and capillary blood were similar to the corresponding total levels in plasma. In vitro both in vivo ciprofloxacin concentration-time profiles were equally effective against select bacterial strains. In conclusion, single-dose administration of two bioequivalent dosage forms of ciprofloxacin might lead to differences in target site pharmacokinetics. These differences, however, are not related to a difference in target site pharmacodynamics.
authors.affiliation: Department of Clinical Pharmacology, University of Vienna Medical School, Austria.
authors.forename: Martin
authors.initials: M
authors.lastname: Brunner
authors.forename: Heino
authors.initials: H
authors.lastname: Stabeta
authors.forename: Jan-Georg
authors.initials: JG
authors.lastname: Möller
authors.forename: Claudia
authors.initials: C
authors.lastname: Schrolnberger
authors.forename: Boban
authors.initials: B
authors.lastname: Erovic
authors.forename: Ursula
authors.initials: U
authors.lastname: Hollenstein
authors.forename: Markus
authors.initials: M
authors.lastname: Zeitlinger
authors.forename: Hans Georg
authors.initials: HG
authors.lastname: Eichler
authors.forename: Markus
authors.initials: M
authors.lastname: Müller
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002939:Ciprofloxacin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D018592:Cross-Over Studies; D006207:Half-Life; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D012463:Saliva / Q000378:metabolism; D014018:Tissue Distribution
chemical_list: D000890:Anti-Infective Agents; D002939:Ciprofloxacin