Glomerular nephrotoxicity of aminoglycosides

Dose-Dependent Amelioration of Gentamicin-Induced Nephrotoxicity in Adult Swiss Albino Rats by Vitamin B-complex - A Preliminary Study

“…It is expected to be safer than the use of a calcium channel blocker or calcium loading. Though complete inhibition of gentamicin toxicity at 3ml/kg body weight/day was way beyond the preliminary hypothesis for this study, amelioration was expected because previous studies have shown significant amelioration of toxicity by prydoxal-6-phosphate (B6) and free radical moppers 1 . It is interesting to note that the amount of vitamin B-complex given to animals in this study (1.5 and 3ml of B-complex) translates to a pyridoxal-6-phosphate dose range of 1.5 to 3mg/kg/body weight while previous studies have shown pyridoxal-6-phosphate to reduce, but not prevent, gentamicin nephrotoxicity at doses above 10mg/kg body weight (usually 100mg/kg body weight) 12,13 .…”

“…Nephrotoxicity and ototoxicity are the most common adverse reactions 1,2 . While nephrotoxicity is almost always reversible due to the regenerating ability of the proximal renal tubules 1 , gentamicin still contributes to an increased incidence of the rather permanent ototoxicity 2 . Various attempts at controlling gentamicin toxicity have been frustrated by lack of a clear understanding of the mechanism of toxicity.…”

“…Various attempts at controlling gentamicin toxicity have been frustrated by lack of a clear understanding of the mechanism of toxicity. Nephrotoxicity has been related to a gentamycin trough concentration above 2µg/ml, calcium deficiency, calcium channel activation, prostaglandins pathways, free radical generation, pyridoxal phosphate deficiency and ascorbic acid depletion 1 . Once daily and extended interval dosing were designed to optimize the concentration-dependent antibiotic activity and essentially timedependent toxicity of gentamicin but the rather wide difference in serum concentrations and the fact that these dosing modes have not been substantiated in pregnancy, paediatric age group and endocarditis, indicate that there are still limitations using these approaches 3 .…”

“…Other attempts at controlling gentamicin toxicity, including the use of pyridoxal phosphate, ascorbic acid, calcium loading, calcium channel blocker, 1 vitamin E 5 and acupuncture 6 have shown either promising or inconsistent results in animals . Those that showed limited efficacy have been difficult to apply clinically due to caution in administering agents that could be toxic themselves or require dose schedules that are not practical in patients 1 .…”

“…Those that showed limited efficacy have been difficult to apply clinically due to caution in administering agents that could be toxic themselves or require dose schedules that are not practical in patients 1 . Hence, an agent that is known to be clinically safe and effective as formulated would be easier to use clinically if found to be effective in ameliorating gentamicin toxicity.…”