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Antimicrobial Agents and Chemotherapy, December 2002, p. 3724-3730, Vol. 46, No. 12
0066-4804/02/$04.00+0     DOI: 10.1128/AAC.46.12.3724-3730.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Target Site Concentrations of Ciprofloxacin after Single Intravenous and Oral Doses

Martin Brunner,1 Heino Staß,2 Jan-Georg Möller,2 Claudia Schrolnberger,1 Boban Erovic,1 Ursula Hollenstein,3 Markus Zeitlinger,1 Hans Georg Eichler,1 and Markus Müller1*

Departments of Clinical Pharmacology,1 Internal Medicine I, Division of Infectious Diseases and Chemotherapy, University of Vienna Medical School, Vienna, Austria,3 BAYER AG, Pharma Research Center, Institute of Clinical Pharmacology, Wuppertal, Germany2

Received 9 April 2001/ Returned for modification 2 December 2001/ Accepted 29 August 2002

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 (AUCinterstitial fluids) were significantly lower than the corresponding AUCplasmas, with AUCinterstitial fluid/AUCplasma ratios ranging from 0.38 to 0.68. For skeletal muscle, the AUCinterstitial 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.

* Corresponding author. Mailing address: Department of Clinical Pharmacology, Division of Clinical Pharmacokinetics, University of Vienna Medical School, Allgemeines Krankenhaus, Währinger Gürtel 18-20, A-1090 Vienna, Austria. Phone: 43-1-40400-2981. Fax: 43-1-40400-2998. E-mail: markus.mueller{at} univie.ac.at.

Antimicrobial Agents and Chemotherapy, December 2002, p. 3724-3730, Vol. 46, No. 12
0066-4804/02/$04.00+0     DOI: 10.1128/AAC.46.12.3724-3730.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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