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Elucidating the relationship between acetazolamide plasma protein binding and renal clearance using an albumin

I H Gomolin1, D J Chapron

  • 1Hebrew Home and Hospital, West Hartford, Connecticut.

Journal of Clinical Pharmacology
|November 1, 1992
PubMed

The effect of plasma protein binding changes on drug clearance is an important concept in clinical pharmacology. In a hypoalbuminemic patient receiving acetazolamide, albumin infusion (50 g) increased acetazolamide plasma protein binding towards normal as the serum albumin concentration rose (r = 0.91, P < .001). The ratio of acetazolamide renal plasma clearance to creatinine clearance decreased as serum albumin levels increased (r = 0.78, P < .05) and the unbound drug fraction fell (r = 0.88, P < .01), but clearance ratios based on unbound plasma acetazolamide levels did not change. Albumin infusion resulted in a nonparallel decline over time between plasma and unbound plasma acetazolamide concentrations. These data demonstrate that, over the range of observed serum albumin concentrations, acetazolamide renal plasma clearance is sensitive to changes in plasma protein binding. Furthermore, our findings emphasize the importance of measuring unbound drug levels when protein binding changes occur during the course of drug disposition studies. Finally, this methodology allows for the fascile assessment of the effects of plasma protein binding changes on renal drug clearance.

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