R. Masereeuw et al., EXCRETION AND ACCUMULATION OF DIATRIZOATE IN THE ISOLATED-PERFUSED RAT-KIDNEY, European journal of pharmaceutical sciences, 5(5), 1997, pp. 295-301
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.