Renal transport of netilmicin in the rat.
We examined the renal transport of [3H]netilmicin in the rat using clearance, microinjection and free flow micropuncture techniques. Netilmicin was constantly infused at rates ranging from 1.92 to 192 nmol/min and resulted in plasma concentrations of 0.4 to 40 micrograms/ml and fractional excretion rates of 94.5 +/- 3.3 to 107.9 +/- 1.7%. Although the mean fractional excretion rate of netilmicin was equal to or exceeded the filtered load, the drug continued to accumulate in renal cortex albeit in a curvilinear manner and at the highest rate of infusion attained a peak level of 447 +/- 26 nmol/g of renal cortex. The renal cortical uptake of netilmicin was inhibited in a dose-dependent fashion by the simultaneous infusion of gentamicin. In response to microinjection of [3H]netilmicin (390 +/- 56 pg) 82.0 +/- 1.8% of the dose was recovered in the urine after early proximal tubular injections, 90.5 +/- 1.1% of the dose was recovered after late proximal tubule injections and 98.5 +/- 1.3% of the dose was recovered after early distal tubule injections. In free flow micropuncture experiments the fractional delivery of netilmicin to the early proximal tubule measured 1.16 +/- 0.03, a value significantly greater than 1.0 (P less than .005). No significant change in fractional delivery was evident to the late proximal tubule (1.13 +/- 0.04), whereas it decreased to 1.02 +/- 0.04 (P less than .01) at the early distal tubule.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D001692:Biological Transport; D004305:Dose-Response Relationship, Drug; D005839:Gentamicins / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism*; D007672:Kidney Cortex / Q000378:metabolism; D007684:Kidney Tubules / Q000378:metabolism; D008297:Male; D008657:Metabolic Clearance Rate; D008845:Microinjections; D009428:Netilmicin / Q000378:metabolism*; D011677:Punctures; D051381:Rats; D011919:Rats, Inbred Strains
D005839:Gentamicins; D009428:Netilmicin