Renal uptake and nephrotoxicity of gentamicin during urinary alkalinization in rats.
1. Effect of urine pH on accumulation of gentamicin in the renal cortex of rats was studied following constant intravenous infusion, and single or repeated i.v. injections with gentamicin. 2. The cortical uptake of gentamicin was moderately inhibited by urinary alkalinization due to sodium bicarbonate treatment, but was unaffected by acidification with ammonium chloride. The altered urinary pH had no effect on urinary excretion of gentamicin. 3. An alkaline urine induced by acetazolamide injections failed to influence cortical accumulation of gentamicin. This effect may be ascribed to 'acidification' of the proximal tubular fluid after carbonic anhydrase inhibition, even though the final urine was alkaline. 4. Nephrotoxicity resulting from chronic treatment of gentamicin was ameliorated by concomitant sodium bicarbonate administration. 5. In conclusion, the intratubular pH of the proximal tubule is a factor which influences the cortical uptake of gentamicin, probably by means of changing the cationic nature of the molecule and, therefore, reduced binding with the luminal membrane.
D000818:Animals; D001639:Bicarbonates / Q000494:pharmacology; D005839:Gentamicins / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006863:Hydrogen-Ion Concentration; D007668:Kidney / Q000378:metabolism*; D007674:Kidney Diseases / Q000139:chemically induced*; D008297:Male; D051381:Rats; D014556:Urine / Q000032:analysis
D001639:Bicarbonates; D005839:Gentamicins