Target organ directed drug delivery: evaluation of renal infusion of chromium-51 ethylenediaminetetraacetate and sodium o-[125I]iodohippurate in the Wistar Kyoto rat

To evaluate the merits of intrarenal drug delivery, the disposition of chromium-51 ethylenediaminetetraacetate (51Cr EDTA) and sodium o-[125I]iodohippurate (125I OIH) was studied following their constant-rate infusion into either the jugular vein or the left or right renal artery of Wistar Kyoto rats. The contralateral kidney was removed. Renal blood flow through the lateral kidney was measured during the experiment via an electromagnetic flow probe. Urine and systemic arterial blood samples were taken at steady state. The clearance and extraction of both substances by the right kidney were independent of the route of administration. Nonlinear kinetics were observed during infusion of 125I OIH at the highest infusion rate in the left kidney. At steady state the advantage of intrarenal over systemic delivery was limited because of the relative high blood flow of the kidney. Only a small reduction (30%) in systemic concentration was achieved by infusion of 51Cr EDTA. Intrarenal infusion of the lower dose (10 nCi/min) of 125I OIH reduced the systemic concentration by greater than 80% when compared with systemic infusion. Intrarenal infusion of the higher dose (40 nCi/min) saturated elimination processes in parts of the left kidney because of nonhomogeneous flow distributio