Renal tubular transport of gentamicin in the rat

Pastoriza-Munoz, Enrique; Bowman, Ralph L.; Kaloyanides, George J.
October 1979
Kidney International;Oct1979, Vol. 16 Issue 4, p440
Academic Journal
The renal handling of gentamicin in the rat was examined by clearance, microinjection, and venal cortical-slice techniques. The steady-state renal clearance of 14C-gentamicin when corrected for the 7.5% binding to plasma protein, was not significantly different from that of all-inulin, At the end of the renal clearance experiments the cortical concentration of gentamicin was 93 ± 7 μg/g of tissue (N = 7), a concentration threefold greater than that of the medulla and 20-fold greater than that of serum. Absorption of ³H-gentamicin along the proximal convoluted tubule and loop of Henle was demonstrated by the tubular microinjection technique. No reabsorption of ³H-gentamicin was detected beyond the early distal convoluted tubule. The tubular absorption of ³H-gentamicin was load dependent. Fractional absorption of ³H-gentamicin averaged 30.1 ± 2.7% when the dose of ³H-gentamicin injected into early proximal tubular convolutions averaged 132 ± 17 pg. It was decreased to 13.6 ± 2.6% when the microinjected dose of gentamicin was increased to 1996 ± 388 pg. No evidence of transtubular absorption of ³H-gentamicin was detected during the microinjection experiments. Microperfusion of peritubular capillaries failed to demonstrate urinary precession of ³H-gentamicin over 14C-inulin, a finding which argues against a rapid transtubular secretory flux of gentamicin. Significant uptake of gentamicin was demonstrated by renal cortical slices incubated in medium containing 14C-gentamicin. The accumulation of 14C-gentamicin by renal conical slices was not inhibited by probenecid or N¹-methylnicotinamide but was inhibited by netilmicin and tobramycin. These data support the conclusion that the renal accumulation of gentamicin reflects transport of gentamicin across both the apical and basolateral membranes of proximal tubular epithelium.


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