Pharmacokinetic-pharmacodynamic relationship of arbekacin for treatment of patients infected with methicillin-resistant Staphylococcus aureus

Reiko Sato, Yusuke Tanigawara, Mitsuo Kaku, Naoki Aikawa, Kihachiro Shimizu

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

Arbekacin is widely used in Japan for the treatment of patients infected with methicillin-resistant Staphylococcus aureus (MRSA). In this study, we have determined the optimal concentration targets of arbekacin for both efficacy and safety. A pharmacokinetic-pharmacodynamic analysis was performed to relate exposure to the drug and clinical cure/improvement or nephrotoxicity. Since we have reported the population pharmacokinetic parameters for arbekacin in the preceding paper (Y. Tanigawara, R. Sato, K. Morita, M. Kaku, N. Aikawa, and K. Shimizu, Antimicrob. Agents Chemother. 50:3754-3762, 2006), individual exposure parameters, such as area under the concentration-time curve (AUC), peak concentration (Cmax), AUC/MIC, Cmax/MIC, and trough concentration (Cmin) were estimated by the Bayesian method. Logistic regression was used to describe the relationship between exposure to the drug and the probability of clinical cure/improvement or nephrotoxicity. For the clinical efficacy analysis, 174 patients confirmed to have an MRSA infection were evaluated. The Cmax, Cmin, and AUC of arbekacin were associated with the probability of clinical cure/improvement during monotherapy. It was shown that the probability of cure/improvement rose when the C max of arbekacin was increased, with an odds ratio of 6.7 for a change in Cmax from 7.9 to 12.5 μg/ml (P = 0.037). For the nephrotoxic risk analysis, 333 patients were included, regardless of whether a pathogen was identified. Logistic regression analysis revealed Cmin and AUC as risk factors of nephrotoxicity (P < 0.005). The estimated probabilities of arbekacin-induced nephrotoxicity were 2.5, 5.2, and 13.1% when the Cmin values were 1, 2, and 5 μg/ml, respectively. The present findings are useful for optimizing the individual dose of arbekacin for the treatment of MRSA-infected patients.

Original languageEnglish
Pages (from-to)3763-3769
Number of pages7
JournalAntimicrobial Agents and Chemotherapy
Volume50
Issue number11
DOIs
Publication statusPublished - 2006 Nov

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Methicillin-Resistant Staphylococcus aureus
Pharmacokinetics
Therapeutics
Logistic Models
Bayes Theorem
habekacin
Pharmaceutical Preparations
Japan
Odds Ratio
Regression Analysis
Safety
Infection
Population

ASJC Scopus subject areas

  • Pharmacology (medical)

Cite this

Pharmacokinetic-pharmacodynamic relationship of arbekacin for treatment of patients infected with methicillin-resistant Staphylococcus aureus. / Sato, Reiko; Tanigawara, Yusuke; Kaku, Mitsuo; Aikawa, Naoki; Shimizu, Kihachiro.

In: Antimicrobial Agents and Chemotherapy, Vol. 50, No. 11, 11.2006, p. 3763-3769.

Research output: Contribution to journalArticle

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