Renal handling of netilmicin in the rat with streptozotocin-induced diabetes mellitus.

ABSTRACT

We examined the hypothesis that the reduced accumulation of aminoglycoside in renal cortex of rats with streptozotocin-induced diabetes mellitus (DM) is secondary to lower rates of tubular transport of drug compared with non-DM rats. Using whole kidney clearance techniques we found that the fractional excretion of [3H]netilmicin in DM rats rose from an initial value of 92.4 +/- 1.3% to 101 +/- 4.5% (N = 10) after eight 20-min periods. These values were not significantly different from those of non-DM rats (96.4 +/- 1.8 and 106.7 +/- 1.4%, respectively, N = 7). The plasma concentration of drug was similar in the two groups whereas inulin clearance and the filtered load of drug were higher in DM rats. In both groups microinjection experiments revealed the presence of an absorptive flux of [3H]netilmicin along the proximal tubule and loop of Henle, but no absorptive flux was detected along the distal nephron. In free-flow micropuncture experiments in DM rats a net secretory flux of netilmicin was detected in the early proximal tubule and a net absorptive flux was detected along the loop of Henle, presumably the pars recta. No net flux occurred along the distal tubule. These findings are similar to those previously reported by us for non-DM rats. At the end of the clearance experiments the concentration of netilmicin in renal cortex of DM rats (56 +/- 5 micrograms/g wet wt.) was significantly less (P less than .01) than that in the renal cortex of non-DM rats (122 +/- 6 micrograms/g wet wt).(ABSTRACT TRUNCATED AT 250 WORDS)