Renal cortical uptake kinetics of gentamicin in rats with impaired renal function.
The renal cortical uptake kinetics of the aminoglycoside antibiotic gentamicin was determined in the remnant kidney model. Renal failure was induced by partial ablation of the right kidney followed by left nephrectomy in female Wistar rats. The animals received a six-hour gentamicin infusion at a constant rate yielding steady-state serum concentrations ranging from 0.5 to 150 micrograms/mL. The renal cortical gentamicin concentrations were determined and related to the serum concentrations achieved. This relationship was nonlinear and followed Michaelis-Menten kinetics. Gentamicin cortical uptake rate, however, did not show clear saturation in the range of gentamicin serum levels studied as was observed in rats with normal renal function. The Michaelis-Menten parameters determined by nonlinear regression were Km = 15.0, 73.9, and 135.7 micrograms/mL; and Vmax = 149.9, 213.7, and 239.2 micrograms/g cortex/h, respectively, for controls, rats with serum creatinine levels between 0.9 and 1.2 mg/dL, and those with levels between 1.3 and 1.8 mg/dL. It is concluded that at serum levels below 100 micrograms/mL, the gentamicin renal cortical uptake is diminished in rats with renal failure. This decrease in renal cortical uptake is more pronounced in the group of rats with more severe renal failure.
D000818:Animals; D003404:Creatinine / Q000378:metabolism; D005260:Female; D005839:Gentamicins / Q000378:metabolism*; D005919:Glomerular Filtration Rate; D007672:Kidney Cortex / Q000378:metabolism*; D007676:Kidney Failure, Chronic / Q000378:metabolism* / Q000503:physiopathology; D007700:Kinetics; D051381:Rats; D011919:Rats, Inbred Strains
D005839:Gentamicins; D003404:Creatinine