Influences of dosage regimen and co-administration of low-molecular weight proteins and basic peptides on renal accumulation of arbekacin in mice

The Journal of Antimicrobial Chemotherapy
Sachiko MurakamiMikihisa Takano

Abstract

The objectives of this study were to characterize renal accumulation of arbekacin, an aminoglycoside antibiotic for treatment of infections with methicillin-resistant Staphylococcus aureus, and to modulate renal uptake of arbekacin, leading to prevention of arbekacin-induced nephrotoxicity. In vivo renal uptake studies were performed using mice. Renal concentrations of arbekacin after a bolus intravenous administration at various doses were analysed by HPLC. In addition, renal concentrations were investigated 24 h after an injection of arbekacin alone or in combination with low-molecular weight proteins and basic peptides. When administered by bolus injection at various doses, renal accumulation of arbekacin showed saturation kinetics with increasing dose. Renal concentration of arbekacin after a bolus administration remained constant from 4 to 24 h and subsequently decreased by a first-order process with a half-life of 42.7 h. The influences of three dosage regimens (a single injection of 4 mg/kg, two injections of 2 mg/kg and three injections of 1.33 mg/kg) were investigated. A single injection resulted in lower renal level of arbekacin than the multiple administrations. Co-administration of cytochrome c, lysozyme and N-WASP1...Continue Reading

Citations

Jan 22, 2013·Clinica Chimica Acta; International Journal of Clinical Chemistry·Autumn R BreaudWilliam Clarke
Jun 12, 2010·Expert Opinion on Drug Metabolism & Toxicology·Junya Nagai, Mikihisa Takano
Feb 20, 2009·Current Opinion in Otolaryngology & Head and Neck Surgery

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