Vol.54 No.1 January 2006
Pharmacokinetic and pharmacodynamic (PK/PD) analysis to determine the optimal method of arbekacin administration
1)Pharmacy of Kitasato University Hospital, 1-15-1 Kitasato, Sagamihara, Kanagawa, Japan
2)Pharmaceutical Science Division, Tokyo University of Pharmacy and Life Science
3)Emergency and Critical Care Medicine, Kitasato University School of Medicine
4)Infectious Diseases, Kitasato University School of Medicine
Abstract
Few large-scale studies have studied the optimal administration of arbekacin (ABK), an anti-MRSA drug. In this study, we compared the efficacy between once and twice daily administrations of ABK in patients with MRSA pneumonia to determine the optimal administration method based on pharmacokinetic (PK) and pharmacodynamic (PD) parameters. The subjects were patients with MRSA pneumonia in whom ABK had been administered at a dose of 200 mg per day and who had been treated between April 1998 and March 2005. All medical records were investigated retrospectively. The serum concentrations at 1 hour after ABK administration on administration days 3 to 7 were defined as the maximum serum concentrations (Cpeak), and the serum concentrations immediately before administration were regarded as the minimum blood concentrations (Ctrough). The endpoints were clinical and bacteriological efficacy and the existence/absence of renal dysfunction. One hundred eleven patients were eligible for analysis. When single and repeated administration regimens were compared using the χ2 test, single administration regimen produced significantly better results and clinical efficacy (p=0.048). In multiple logistic regression analyses, the significant index for clinical efficacy was Cpeak [p=0.008, Odds ratio (OR) =1.27, 95% confidential interval (95%CI) =1.06-1.57], that for bacteriological efficacy was Cpeak/MIC [p=0.016, OR=1.22, 95%CI=1.04-1.77], and those for onset of renal dysfunction were Ctrough [p=0.002, OR=2.00, 95%CI=1.32-3.34] and patient's age [p=0.046, OR=1.06, 95%CI=1.01-1.14]. A target Ctrough value according to age should be established to prevent renal dysfunction. Further studies are required to establish the upper limit of the Cpeak value.
Key word
arbekacin, MRSA, optimal dosage, PK/PD analysis
Received
September 29, 2005
Accepted
November 21, 2005
Jpn. J. Chemother. 54 (1): 18-24, 2006
