The effect of guanidine on the accumulation of amikacin in guinea pig renal cortical slices.
The role of a recently identified organic ion transport system in the accumulation of the aminoglycoside (AG), amikacin (AK) in the kidney was investigated in the present study. Because this transport system has been characterized as being a carrier for the organic cation, guanidine, the effect of guanidine on the uptake of AK into renal slices from guinea pig was examined. Renal slices incubated in medium containing AK concentrated the drug against a concentration gradient (i.e. slice:medium ratio (S/M) greater than 1.0). This uptake was significantly reduced when an equimolar concentration (1 x 10(-5) M) of another AG, gentamicin was added to the incubation medium. In contrast, AK uptake was relatively insensitive to the presence of the cation, tetraethylammonium (TEA) in the medium. Guanidine was also ineffective at inhibiting AK uptake into slices and reduced AK uptake by only 22% at guanidine concentrations of 1 x 10(-2) M. In comparison, TEA was slightly more sensitive to the presence of guanidine in the incubation media since TEA uptake was reduced by 22% at guanidine concentrations of 1 x 10(-3) M and reduced by approximately 70% at guanidine concentrations of 1 x 10(-2) M. Thus, the results of the present study suggest that the guanidine transport system does not play a role in the renal accumulation of AK since the presence of guanidine in the incubation medium had little effect on the accumulation of AK into renal cortical slices.
Suzuki
C A
CA
Bureau of Drug Research, Sir F.G. Banting Research Centre, Ottawa, Canada.
Thomas
B H
BH
D000583:Amikacin / Q000493:pharmacokinetics*; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D005839:Gentamicins / Q000494:pharmacology; D019791:Guanidine; D006146:Guanidines / Q000494:pharmacology*; D006168:Guinea Pigs; D007672:Kidney Cortex / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D013757:Tetraethylammonium Compounds / Q000493:pharmacokinetics / Q000494:pharmacology; D010130:p-Aminohippuric Acid / Q000493:pharmacokinetics
D005839:Gentamicins; D006146:Guanidines; D013757:Tetraethylammonium Compounds; D000583:Amikacin; D019791:Guanidine; D010130:p-Aminohippuric Acid