Protective effect of inactive ingredients against nephrotoxicity of vancomycin hydrochloride in rats.
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.
Hodoshima
Naoko
N
Toxicology & Pharmacokinetics Research Labs., Pharmaceutical Development Department, Meiji Seika Kaisha, Ltd. Naoko_Hodoshima@meiji.co.jp
Nakano
Yoshihisa
Y
Izumi
Masaaki
M
Mitomi
Nayu
N
Nakamura
Yukari
Y
Aoki
Makoto
M
Gyobu
Akiko
A
Shibasaki
Shigeki
S
Kurosawa
Toru
T
D000818:Animals; D000900:Anti-Bacterial Agents / Q000097:blood / Q000737:chemistry / Q000633:toxicity* / Q000652:urine; D004355:Drug Stability; D005079:Excipients / Q000737:chemistry*; D007275:Injections, Intravenous; D007668:Kidney / Q000187:drug effects* / Q000473:pathology; D008297:Male; D008353:Mannitol / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D014640:Vancomycin / Q000097:blood / Q000737:chemistry / Q000633:toxicity* / Q000652:urine
D000900:Anti-Bacterial Agents; D005079:Excipients; D008353:Mannitol; D011092:Polyethylene Glycols; D014640:Vancomycin