Hodoshima Naoko, Nakano Yoshihisa, Izumi Masaaki, Mitomi Nayu, Nakamura Yukari, Aoki Makoto, Gyobu Akiko, Shibasaki Shigeki, Kurosawa Toru
Toxicology & Pharmacokinetics Research Labs., Pharmaceutical Development Department, Meiji Seika Kaisha, Ltd.
Drug Metab Pharmacokinet. 2004 Feb;19(1):68-75. doi: 10.2133/dmpk.19.68.
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.
一种用于静脉输注的万古霉素通用型制剂（MEEK），由于添加了两种非活性成分：D - 甘露醇和聚乙二醇400（PEG400），其溶解度和稳定性均高于品牌名为盐酸万古霉素（VCM）的制剂。本研究的目的是比较MEEK与品牌名VCM（S - VCM）的肾毒性，并分析这些制剂的药代动力学。以40mg/kg的临床剂量给大鼠给药后，MEEK和S - VCM在药代动力学及对肾脏的影响方面没有差异，这表明MEEK应与S - VCM一样有效。当以400mg/kg的肾毒性剂量给药时，S - VCM导致肾功能损害和肾脏损伤，并且由于肾清除率降低观察到血浆浓度升高。相比之下，MEEK对肾功能或肾脏几乎没有影响，也未引起肾清除率的明显变化。这些发现表明，MEEK中的非活性成分在降低VCM的肾毒性方面发挥了作用。
