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 protein concentrations (0.25, 0.5, 0.75, 1.0, 4.0 and 6.0 g/100 ml) and an initial drug concentration of 100 micrograms/ml. Kidney viability was within 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 finding contradicted conventional wisdom regarding extraction ratio and renal elimination, the results were consistent with a proposed ancillary role of albumin in renal tubular transport processes. An alternative clearance model was developed, analogous to earlier models of hepatic elimination. The facilitated renal clearance model utilized and validated in this investigation represents a composite of previously proposed theories, modified to account for albumin-mediated tubular secretion.
Taft
D R
DR
School of Pharmacy, University of Connecticut, Storrs, USA.
Sweeney
K R
KR
D000086:Acetazolamide / Q000493:pharmacokinetics*; D000818:Animals; D001692:Biological Transport; D007668:Kidney / Q000378:metabolism*; D007684:Kidney Tubules / Q000378:metabolism*; D008297:Male; D008657:Metabolic Clearance Rate; D010477:Perfusion; D011485:Protein Binding; D051381:Rats; D017207:Rats, Sprague-Dawley; D012709:Serum Albumin / Q000378:metabolism*
D012709:Serum Albumin; D000086:Acetazolamide