Paracetamol metabolism by the isolated perfused rat kidney

Abstract

Renal metabolism of drugs and their effects on tubular function depend on the entry of the drug into specific renal cells. In turn, this depends on differential regional blood flow and the relative rates of delivery of the drug to luminal and contraluminal surfaces of the cell following filtration at the glomerulus. In studies of renal pharmacology, it is desirable to have an intact kidney with a clearly defined experimental system. Such conditions are provided in part by the isolated perfused rat kidney, in which a buffered, oxygenated medium containing only bovine serum albumin in Krebs-Henseleit saline is perfused into the renal artery. Glomerular filtration, fractional sodium reabsorption, and the composition of the recirculated perfusate, as well as the urine and the kidney itself, can all be analyzed. Bowman [1] has recently outlined the perfusion methods relevant to pharmacology. This paper briefly reviews the approaches to renal drug handling and drug effects using the isolated perfused kidney. Its main purpose is to report detailed studies with tritiated paracetamol demonstrating direct renal involvement in metabolism of this drug and to offer possible mechanisms for the development of analgesic nephropathy and nephrotoxicity of other drugs.