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Antimicrobial Agents and Chemotherapy, November 2006, p. 3754-3762, Vol. 50, No. 11
0066-4804/06/$08.00+0     doi:10.1128/AAC.00420-05
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Population Pharmacokinetics of Arbekacin in Patients Infected with Methicillin-Resistant Staphylococcus aureus

Yusuke Tanigawara,1* Reiko Sato,1 Kunihiko Morita,1 Mitsuo Kaku,2 Naoki Aikawa,3 and Kihachiro Shimizu4

Department of Pharmacy, Keio University Hospital, Tokyo, Japan,1 Division of Molecular Diagnostics, Department of Clinical Medicine, Tohoku University, Graduate School of Medicine, Sendai, Japan,2 Department of Emergency and Critical Care Medicine, Keio University Hospital, Tokyo, Japan,3 The Kitasato Institute, Tokyo, Japan4

Received 2 April 2005/ Returned for modification 23 June 2005/ Accepted 23 December 2005

Arbekacin, a derivative of dibekacin, is an aminoglycoside developed and widely used in Japan for the treatment of patients infected with methicillin-resistant Staphylococcus aureus (MRSA). The population pharmacokinetics of arbekacin was investigated in the Japanese, using 353 patients infected with MRSA and 50 healthy or renally impaired volunteers. The age of the study population ranged from 8 to 95 years, and weight ranged from 10.8 to 107 kg. In total, 1,581 serum arbekacin concentrations were measured (primarily from routine patient care) and used to perform the present pharmacokinetic analysis. Drug concentration-time data were well described by a two-compartment open model. Factors influencing arbekacin pharmacokinetics were investigated using a nonlinear mixed-effect model analysis. The best-developed model showed that drug clearance (CL) was related to creatinine clearance (CLCR), age, and body weight (WT), as expressed by CL (liter/h) = 0.0319CLCR + (26.5/age) (CLCR < 80 ml/min) and CL (liter/h) = 0.0130 CLCR + 0.0342WT + (26.5/age) (CLCR ≥ 80 ml/min). The volume of distribution for the central and peripheral compartments was different in healthy subjects and infected patients, and this difference was more pronounced among disease types. The elderly subjects (aged 80 years or over) exhibited, on average, a 19% greater volume for the central compartment. The volumes for the peripheral compartment were 50.6 liters in patients with pneumonia and 24.3 liters in patients with sepsis. The population pharmacokinetic parameters of arbekacin obtained here are useful for optimal use of this aminoglycoside in the treatment of MRSA-infected patients.

* Corresponding author. Mailing address: Department of Hospital Pharmacy, School of Medicine, Keio University, Tokyo 160-8582, Japan. Phone: 81-(0)3-5363-3847. Fax: 81-(0)3-5269-4576. E-mail: tanigawa{at}sc.itc.keio.ac.jp.

Antimicrobial Agents and Chemotherapy, November 2006, p. 3754-3762, Vol. 50, No. 11
0066-4804/06/$08.00+0     doi:10.1128/AAC.00420-05
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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  • Sato, R., Tanigawara, Y., Kaku, M., Aikawa, N., Shimizu, K. (2006). Pharmacokinetic-Pharmacodynamic Relationship of Arbekacin for Treatment of Patients Infected with Methicillin-Resistant Staphylococcus aureus. Antimicrob. Agents Chemother. 50: 3763-3769 [Abstract] [Full Text]  


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