[Nephrotoxicity and drug interaction of vancomycin].
We examined drug interactions of vancomycin hydrochloride (VCM) in the rabbit kidney. VCM has an antibacterial action against Gram positive bacteria, but composite infection patients must be jointly treated with antibiotics that are effective on Gram negative bacteria, e.g., imipenem (IPM)-cilastatin sodium (CS) compounding agent. Both VCM and IPM have the adverse reaction of nephrotoxicity, whereas CS restrains the nephrotoxicity of IPM. To clarify the interactions, we examined the nephrotoxicity and pharmacokinetics of VCM in the rabbit and compared them with those in rabbits administered VCM with CS or IPM-CS. Symptoms of nephrotoxicity such as an increase of serum creatinine concentration and BUN and a morphological change of the kidney were observed with iv. injection of VCM at 300 mg/kg. However, no abnormality of clinical data and morphological alteration were observed in the groups injected with VCM plus CS or IPM-CS. Clearance and urinary excretion of VCM obviously increased in the groups injected with VCM plus CS or IPM-CS. In addition, it was estimated that VCM was actively transported by observation of the uptake in rabbit renal slices. Furthermore, the uptake rate of VCM in the renal cortex was significantly decreased by CS. Together with the above findings, it is suggested that the restraint effect of VCM uptake into nephrocytes by CS is one of the decreasing mechanisms of the nephrotoxic effect of VCM.
Toyoguchi
T
T
Department of Pharmacy, Yamagata University School of Medicine, Japan.
Nakagawa
Y
Y
Watanabe
H
H
D000818:Animals; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics / Q000633:toxicity*; D015377:Cilastatin / Q000494:pharmacology; D004347:Drug Interactions; D004359:Drug Therapy, Combination / Q000493:pharmacokinetics / Q000633:toxicity; D015378:Imipenem / Q000493:pharmacokinetics / Q000633:toxicity; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D011480:Protease Inhibitors / Q000494:pharmacology; D011817:Rabbits; D013845:Thienamycins / Q000493:pharmacokinetics / Q000633:toxicity; D014640:Vancomycin / Q000493:pharmacokinetics / Q000633:toxicity*
D000900:Anti-Bacterial Agents; D011480:Protease Inhibitors; D013845:Thienamycins; D015377:Cilastatin; D014640:Vancomycin; D015378:Imipenem