Intrarenal concentrations of doxycycline were measured in 48 normal canine kidneys during wide variations in urine pH and the systemic state of hydration of the experimental animals. The results were compared with the renal parenchymal levels achieved in 10 severely diseased human kidneys. Although the state of hydration, the urine pH, and renal disease all significantly influenced the urinary concentrations and rate of renal clearance of doxycycline, there was no detectable difference between concentrations in normal renal tissue and those in severely diseased kidneys. This result is in contradistinction of the findings for previously evaluated antibiotics. The levels of doxycycline measured in renal tissue averaged twice the concentration in serum without notable difference among levels in renal cortex, medulla, and papilla. Prospective clinical trials will be necessary for identification of any solid correlation between the remarkable characteristics of accumulation of doxycycline in diseased renal parenchymal tissue and the clinical, therapeutic importance of such an observation.
Dibekacin (3',4-dideoxykanamycin B) is a new semisynthetic aminoglycoside developed in Japan and one which has found wide clinical acceptance in that country. The antibacterial activity of this compound indicates that it is relatively similar to gentamicin. Since it appears that the intrarenal distributional characteristics and renal cortical kinetics of aminoglycosides provide some predictive information concerning the clinical incidence of nephrotoxicity, we designed a series of pharmacokinetic studies in healthy mongrel dogs which would define such kinetic information for dibekacin and would contrast the results with similar studies for gentamicin and tobramycin. The renal cortical kinetics of dibekacin, as developed in these studies, show that in a canine model the behavior of dibekacin is similar to that of gentamicin and significantly different from tobramycin. Dibekacin and gentamicin show reproducibly higher renal cortical tissue concentrations than tobramycin in both the acute infusion studies and multiple dosing studies. The results suggest that dibekacin may possess the same inherent nephrotoxic potential as that of gentamicin. In order to show any difference in clinical toxicity between gentamicin and dibekacin, a very extensive randomized, double-blind, prospective clinical trial of efficacy and toxicity will be needed.
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