Renal tubular transport of gentamicin in the rat

Renal tubular transport of gentamicin in the rat. The renal handling of gentamicin in the rat was examined by clearance, microinjection, and renal cortical-slice techniques. The steady-state renal clearance of 14 C-gentamicin, when corrected for the 7.5% binding to plasma protein, was not significantly different from that of 3 H-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 3 H-gentamicin along the proximal convoluted tubule and loop of Henle was demonstrated by the tubular microinjection technique. No reabsorption of 3 H-gentamicin was detected beyond the early distal convoluted tubule. The tubular absorption of 3 H-gentamicin was load dependent. Fractional absorption of 3 H-gentamicin averaged 30.1 ± 2.7% when the dose of 3 H-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 3 H-gentamicin was detected during the microinjection experiments. Microperfusion of peritubular capillaries failed to demonstrate urinary precession of 3 H-gentamicin over 14 C-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 14 C-gentamicin. The accumulation of 14 C-gentamicin by renal cortical slices was not inhibited by probenecid or N 1 -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. Transport tubulaire de la gentamicine chez le rat. Le transport tubulaire de la gentamicine chez le rat a ete etudie au moyen des techniques de clearance, de micro-injection et de tranches de cortex. La clearance de la 14 C-gentamicine a l'etat stationnaire, corrigee pour la liaison aux proteines plasmatiques de 7,5%, n'est pas significativement differente de celle de l'inuline. A la fin des experiences de clearances la concentration corticale de la gentamicine est de 93 ± 7 µg/g de tissu (N = 7), trois fois plus que dans la medullaire et vingt fois plus que dans le plasma. L'absorption de gentamicine tritiee le long du tube contourne proximal et dans l'anse de Henle a pu etre demontree par la technique de microinjections tubulaires. Aucune reabsorption de gentamicine tritiee n'a ete constatee en aval du tube contourne distal initial. Cette absorption tubulaire est dependante de la charge. L'absorption fractionnelle de gentamicine tritiee est en moyenne de 30,1 ± 2,7% quand la quantite injectee dans le tube proximal precoce est de 132 ± 17 pg. Elle diminue a 13,6 ± 2,6% quand la quantite injectee augmente a 1996 ± 388 pg. Aucune preuve de passage transtubulaire de gentamicine tritiee n'a ete obtenue au cours des experiences de microinjections. La microperfusion des capillaires peritubulaires n'a pas permis de mettre en evidence une precession de la gentamicine tritiee sur l'inuline 14 C, une constatation qui plaide contre un flux secretoire transtubulaire rapide. Une captation significative de gentamicine a ete mise en evidence par l'incubation de tranches de cortex dans un milieu contenant de la gentamicine 14 C. L'accumulation de 14 C-gentamicine par les tranches de cortex renal n'est pas inhibee par le probenecid ou le N 1 -methylnicotinamide mais l'est par la netilmycine et la tobramycine. Ces observations sont en faveur du fait que l'accumulation renale de gentamicine reflete son transport a la fois a travers la membrane apicale et la membrane basolaterale de l'epithelium tubulaire proximal.