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Antimicrobial Agents and Chemotherapy, May 2009, p. 2074-2081, Vol. 53, No. 5
0066-4804/09/$08.00+0     doi:10.1128/AAC.01056-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Penetration of Moxifloxacin into Bone Evaluated by Monte Carlo Simulation{triangledown}

Cornelia B. Landersdorfer,1,§ Martina Kinzig,1 Friedrich F. Hennig,2 Jürgen B. Bulitta,1,§ Ulrike Holzgrabe,3 George L. Drusano,4 Fritz Sörgel,1,5* and Johannes Gusinde2

IBMP—Institute for Biomedical and Pharmaceutical Research, Nürnberg-Heroldsberg, Germany,1 Department of Surgery, University of Erlangen, Erlangen, Germany,2 Institute of Pharmacy and Food Chemistry, University of Würzburg, Würzburg, Germany,3 Ordway Research Institute, Albany, New York,4 Department of Pharmacology, University of Duisburg-Essen, Essen, Germany5

Received 5 August 2008/ Returned for modification 10 November 2008/ Accepted 2 February 2009

Moxifloxacin is a fluoroquinolone with a broad spectrum of activity and good penetration into many tissues, including bone. Penetration of moxifloxacin into bone has not yet been studied using compartmental modeling techniques. Therefore, we determined the rate and extent of bone penetration by moxifloxacin and evaluated its pharmacodynamic profile in bone via Monte Carlo simulation. Twenty-four patients (10 males, 14 females) undergoing total hip replacement received 400 mg moxifloxacin orally 2 to 7 h prior to surgery. Blood and bone specimens were collected. Bone samples were pulverized under liquid nitrogen by a cryogenic mill, including an internal standard. Drug concentrations were analyzed by high-performance liquid chromatography. We used ADAPT II (results reported), NONMEM, and WinBUGS for pharmacokinetic analysis. Monte Carlo simulation was performed to reverse engineer the necessary area under the free concentration-time curve fAUCSERUM/MIC in serum and total AUCBONE/MIC in bone for a successful clinical or microbiological outcome. The median (10% to 90% percentile for between-subject variability) of the AUC in bone divided by the AUC in serum (AUCBONE/AUCSERUM) was 80% (51 to 126%) for cortical bone and 78% (42 to 144%) for cancellous bone. Equilibration between serum and bone was rapid. Moxifloxacin achieved robust (≥90%) probabilities of target attainment (PTAs) in serum, cortical bone, and cancellous bone up to MICs of ≤0.375 mg/liter based on the targets fAUCSERUM/MIC ≥ 40 and AUCBONE/MIC ≥ 33. Moxifloxacin showed high bone concentrations and a rapid equilibrium between bone and serum. The favorable PTAs compared to the 90%-inhibitory MIC of Staphylococcus aureus warrant future clinical trials on the effectiveness of moxifloxacin in the treatment of bone infections.

* Corresponding author. Mailing address: IBMP—Institute for Biomedical and Pharmaceutical Research, Paul-Ehrlich-Str. 19, D-90562 Nürnberg-Heroldsberg, Germany. Phone: 49-911-518290. Fax: 49-911-5182920. E-mail: ibmp{at}osn.de

{triangledown} Published ahead of print on 17 February 2009.

§ Present address: Department of Pharmaceutical Sciences, State University of New York at Buffalo, Buffalo, NY 14260.

Antimicrobial Agents and Chemotherapy, May 2009, p. 2074-2081, Vol. 53, No. 5
0066-4804/09/$08.00+0     doi:10.1128/AAC.01056-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Landersdorfer, C. B., Kinzig, M., Bulitta, J. B., Hennig, F. F., Holzgrabe, U., Sorgel, F., Gusinde, J. (2009). Bone Penetration of Amoxicillin and Clavulanic Acid Evaluated by Population Pharmacokinetics and Monte Carlo Simulation. Antimicrob. Agents Chemother. 53: 2569-2578 [Abstract] [Full Text]  


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