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Updated: Aug 21, 2026

Intravascular Delivery of Biologics to the Rat Kidney
Published on: September 1, 2016
Protective effect of inactive ingredients against nephrotoxicity of vancomycin hydrochloride in rats
Naoko Hodoshima1, Yoshihisa Nakano, Masaaki Izumi
1Toxicology & Pharmacokinetics Research Labs., Pharmaceutical Development Department, Meiji Seika Kaisha, Ltd. Naoko_Hodoshima@meiji.co.jp
Abstract:
A generic form of vancomycin for I.V. infusion (MEEK) is more soluble and stable than the brand-name form of vancomycin hydrochloride (VCM) due to the addition of two inactive ingredients: D-mannitol and Macrogol400 (PEG400). The aim of the present study was to compare the nephrotoxicity of MEEK with that of brand-name VCM (S-VCM) and to analyze the pharmacokinetics of these preparations. Following administration to rats at the clinical dose of 40 mg/kg, there was no difference between MEEK and S-VCM with regard to pharmacokinetics and effects on the kidneys, indicating that MEEK should be as effective as S-VCM. When administered at the nephrotoxic dose of 400 mg/kg, S-VCM caused impairment of renal function and kidney damage, and an increase of the plasma concentration due to decreased renal clearance was observed. In contrast, MEEK had virtually no effect on renal function or the kidneys and did not cause a marked change of renal clearance. These findings suggest that the inactive ingredients in MEEK play a role in reducing the nephrotoxicity of VCM.
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