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Antimicrobial Agents and Chemotherapy, October 1999, p. 2345-2349, Vol. 43, No. 10
0066-4804/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Penetration of Moxifloxacin into Peripheral Compartments in Humans

Markus Müller,1,* Heino Staß,2 Martin Brunner,1 Jan G. Möller,2 Edith Lackner,1 and Hans G. Eichler1

Department of Clinical Pharmacology, Section of Clinical Pharmacokinetics, Vienna University School of Medicine, Vienna, Austria,1 and The Bayer Pharma Research Center, Institute of Clinical Pharmacology, Wuppertal, Germany2

Received 17 November 1998/Returned for modification 31 March 1999/Accepted 1 July 1999

To characterize the penetration of moxifloxacin (BAY 12-8039) into peripheral target sites, the present study aimed at measuring unbound moxifloxacin concentrations in the interstitial space fluid by means of microdialysis, an innovative clinical sampling technique. In addition, moxifloxacin concentrations were measured in cantharides-induced skin blisters, saliva, and capillary plasma and compared to total- and free-drug concentrations in venous plasma. For this purpose, 12 healthy volunteers received moxifloxacin in an open randomized crossover fashion either as a single oral dose of 400 mg or as a single intravenous infusion of 400 mg over 60 min. An almost-complete equilibration of the free unbound plasma fraction of moxifloxacin with the interstitial space fluid was observed, with mean area under the concentration-time curve (AUC)interstitial fluid/AUCtotal-plasma ratios ranging from 0.38 to 0.55 and mean AUCinterstitial fluid/AUCfree-plasma ratios ranging from 0.81 to 0.86. The skin blister concentration/plasma concentration ratio reached values above 1.5 after 24 h, indicating a preferential penetration of moxifloxacin into inflamed lesions. The moxifloxacin concentrations in saliva and capillary blood were similar to the corresponding levels in plasma. Our data show that moxifloxacin concentrations attained in the interstitial space fluid in humans and in skin blister fluid following single doses of 400 mg exceed the values for the MIC at which 90% of isolates are inhibited for most clinically relevant bacterial strains, notably including penicillin-resistant Streptococcus pneumoniae. These findings support the use of moxifloxacin for the treatment of soft tissue and respiratory tract infections in humans.

* Corresponding author. Mailing address: Department of Clinical Pharmacology, Section of Clinical Pharmacokinetics, Vienna University School of Medicine, Währinger Gürtel 18-20, A-1090 Vienna, Austria. Phone: 43-1-40400/2980. Fax: 43-1-40400/2998. E-mail: markus.mueller{at}univie.ac.at.

Antimicrobial Agents and Chemotherapy, October 1999, p. 2345-2349, Vol. 43, No. 10
0066-4804/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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