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Antimicrobial Agents and Chemotherapy, October 2005, p. 4149-4153, Vol. 49, No. 10
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.10.4149-4153.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Increase of Microcirculatory Blood Flow Enhances Penetration of Ciprofloxacin into Soft Tissue

Christian Joukhadar,1,2* Pejman Dehghanyar,1 Friederike Traunmüller,1 Robert Sauermann,1 Bernhard Mayer-Helm,1 Apostolos Georgopoulos,2 and Markus Müller1

Department of Clinical Pharmacology, Division of Clinical Pharmacokinetics,1 Department of Internal Medicine I, Division of Infectious Disease and Chemotherapy, Medical University of Vienna, Vienna, Austria2

Received 27 February 2005/ Returned for modification 11 April 2005/ Accepted 11 July 2005

The present study addressed the effect of microcirculatory blood flow on the ability of ciprofloxacin to penetrate soft tissues. Twelve healthy male volunteers were enrolled in an analyst-blinded, clinical pharmacokinetic study. A single intravenous dose of 200 mg of ciprofloxacin was administered over a period of approximately 20 min. The concentrations of ciprofloxacin were measured in plasma and in the warmed and contralateral nonwarmed lower extremities. The microdialysis technique was used for the assessment of unbound ciprofloxacin concentrations in subcutaneous adipose tissue. Microcirculatory blood flow was measured by use of laser Doppler flowmetry. Warming of the extremity resulted in an increase of microcirculatory blood flow by approximately three- to fourfold compared to that at the baseline (P < 0.05) in subcutaneous adipose tissue. The ratio of the maximum concentration (Cmax) of ciprofloxacin for the warmed thigh to the Cmax for the nonwarmed thigh was 2.10 ± 0.90 (mean ± standard deviation; P < 0.05). A combined in vivo pharmacokinetic (PK)-in vitro pharmacodynamic (PD) simulation based on tissue concentration data indicated that killing of Pseudomonas aeruginosa (ATCC 27853 and two clinical isolates) was more effective by about 2 log10 CFU/ml under the warmed conditions than under the nonwarmed conditions (P < 0.05). The improvement of microcirculatory blood flow due to the warming of the extremity was paralleled by an increased ability of ciprofloxacin to penetrate soft tissue. Subsequent PK-PD simulations based on tissue PK data indicated that this increase in tissue penetration was linked to an improved antimicrobial effect at the target site.

* Corresponding author. Mailing address: Department of Clinical Pharmacology, Division of Clinical Pharmacokinetics, Waehringer Guertel 18-20, Vienna 1090, Austria. Phone: 43-1-40400/2981. Fax: 43-1-40400/2998. E-mail: christian.joukhadar{at}meduniwien.ac.at.

Antimicrobial Agents and Chemotherapy, October 2005, p. 4149-4153, Vol. 49, No. 10
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.10.4149-4153.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Schmidt, S., Banks, R., Kumar, V., Rand, K. H., Derendorf, H. (2008). Clinical Microdialysis in Skin and Soft Tissues: An Update. J Clin Pharmacol 48: 351-364 [Abstract] [Full Text]  


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