THE INFLUENCE OF PROTEIN-BINDING ON THE ELIMINATION OF ACETAZOLAMIDE BY THE ISOLATED-PERFUSED RAT-KIDNEY - EVIDENCE OF ALBUMIN-MEDIATED TUBULAR SECRETION

The impact of albumin on the renal elimination of acetazolamide, a low extraction ratio compound, was investigated in the isolated perfused rat kidney. Perfusion studies were conducted over a wide range of prot ein concentrations (0.25, 0.5, 0.75, 1.0, 4.0 and 6.0 g/100 ml) and an initial drug concentration of 100 mu g/ml. Kidney viability was withi n normal limits among all treatment groups. Over the range of albumin levels studied, an approximate 3.4-fold increase in drug-free fraction effected a 2.8-fold increase in renal clearance. Although this findin g contradicted conventional wisdom regarding extraction ratio and rena l elimination, the results were consistent with a proposed ancillary r ole of albumin in renal tubular transport processes. An alternative cl earance model was developed, analogous to earlier models of hepatic el imination. The facilitated renal clearance model utilized and validate d in this investigation represents a composite of previously proposed theories, modified to account for albumin-mediated tubular secretion.