THE INFLUENCE OF PROTEIN-BINDING ON THE ELIMINATION OF ACETAZOLAMIDE BY THE ISOLATED-PERFUSED RAT-KIDNEY - EVIDENCE OF ALBUMIN-MEDIATED TUBULAR SECRETION
Dr. Taft et Kr. Sweeney, THE INFLUENCE OF PROTEIN-BINDING ON THE ELIMINATION OF ACETAZOLAMIDE BY THE ISOLATED-PERFUSED RAT-KIDNEY - EVIDENCE OF ALBUMIN-MEDIATED TUBULAR SECRETION, The Journal of pharmacology and experimental therapeutics, 274(2), 1995, pp. 752-760
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.