EXCRETION AND ACCUMULATION OF DIATRIZOATE IN THE ISOLATED-PERFUSED RAT-KIDNEY

The present study was designed to investigate the renal disposition of diatrizoate in the isolated perfused rat kidney (IPK). To the IPK, 5 different doses were added (between 1.13 and 44 mg), resulting in init ial perfusate concentrations between 4.5 and 175 mu g/ml. At all perfu sate concentrations, the renal excretion rate of diatrizoate was signi ficantly lower than the filtration rate, indicating that a reabsorptiv e mechanism is involved in renal diatrizoate handling. The ratio of di atrizoate clearance over GFR (Cl-R/GF) was 0.67 +/- 0.04 at 4.5 mu g/m l, and increased slightly to 0.76 +/- 0.03 at 175 mu g/ml, suggesting that tubular reabsorption is mediated by a saturable mechanism. Accumu lation of diatrizoate in kidney tissue was significantly reduced after preincubation of the perfused kidneys with the organic anion transpor t inhibitor probenecid, whereas renal clearance was not affected. At a n initial perfusate concentration of 4.5 mu g/ml a kidney-to-perfusate ratio (K/P-ratio) of 2.5 +/- 0.9 was found, which decreased to 1.3 +/ - 0.2 after preincubation with probenecid. At a perfusate concentratio n of 47 mu g/ml a K/P-ratio of 1.4 +/- 0.3 was determined, which incre ased significantly to 2.5 +/- 0.4 at a concentration of 175 mu g/ml. W e suggest that this unusual profile in concentration-dependent accumul ation may be explained by a renal clearance mechanism for diatrizoate that consists of saturable reabsorption in conjunction with active tub ular secretion. (C) 1997 Elsevier Science B.V.