Renal handling and lymph concentration of tetroxoprim and metioprim: an experimental study in dogs.

The renal handling and renal lymph concentrations of tetroxoprim and metioprim, 2 trimethoprim analogs, were investigated during constant intravenous infusion in 8 dogs. The mean ratios of tetroxoprim and metioprim clearance to creatinine clearance were 0.40 and 0.16 respectively. After compensation for protein binding, both antimicrobials were found to undergo a renal tubular net reabsorption of 55 to 60 per cent of the filtered amount. Renal lymph was obtained by direct cannulation of capsular lymphatics, and the mean lymph-to-arterial plasma concentration ratios were 0.93 and 0.74 for tetroxoprim and metioprim, respectively. Renal tissue concentrations of the 2 microbials were many times higher than the simultaneous concentrations in plasma, suggesting that lymph concentrations do not represent the entire interstitial compartment or that significant amounts of antimicrobial are located intracellularly. Tetroxoprim and metioprim concentrated well in the kidney, but their potential use in the treatment of pyelonephritis awaits verification in clinical trials.