Relationship between renal clearance, protein binding and urine flow for digitoxin, a compound of low clearance in the isolated perfused rat kidney.

An isolated perfused rat kidney preparation is described which allows the relationship between protein binding and renal clearance to be studied in a quantitative manner. The influence of unbound fraction of drug in the perfusate, urine pH and urine flow upon the renal clearance of digitoxin is examined. Renal clearance and unbound fraction were found to be related linearly. Urine pH did not influence digitoxin renal clearance but urine flow did, in a nonlinear manner. A simple physiologically based model of renal clearance is developed which predicts the influence of urine flow and protein binding upon digitoxin clearance in this preparation.