Disopyramide protein binding in plasma from patients with nephrotic syndrome during the exacerbation and remission phases.

Abstract

1 Plasma protein binding of disopyramide was determined twice in plasma from seven patients with severe nephrotic syndrome when the disease activity was markedly different for each patient (mean +/- s.d. of serum albumin 21 +/- 4 vs 29 +/- 3 g l-1 (P less than 0.05), proteinuria 13.6 +/- 9.6 vs 2.2 +/- 1.7 g day-1 (P less than 0.01), and alpha 1-acid glycoprotein 0.34 +/- 0.12 vs 0.95 +/- 0.28 g l-1 (P less than 0.01) during the exacerbation vs remission phases, respectively). 2 Plasma samples containing disopyramide at the concentrations of 0.2-12.0 micrograms ml-1 were analysed by ultrafiltration. The free fractions at the proposed therapeutic concentration range (2.0-6.0 micrograms ml-1) were significantly (P less than 0.01) greater during the exacerbation phase than during the remission phase. 3 Multiple linear regression analysis revealed that the free fraction of disopyramide at 3.0 micrograms ml-1 correlated much better with alpha 1-acid glycoprotein (partial correlation coefficient = 0.85, P less than 0.01) than with albumin (partial correlation coefficient = 0.25, P less than 0.05). 4 The binding data of disopyramide analysed by a model assuming one specific binding site and nonspecific binding(s) demonstrated that the capacity constant correlated significantly (r = 0.97, P less than 0.001) with plasma alpha 1-acid glycoprotein. 5 The results suggest that a total concentration of disopyramide within the therapeutic range may not be a reliable guide for a safe dosing scheme in patients with severe nephrotic syndrome, particularly during the exacerbation period.(ABSTRACT TRUNCATED AT 250 WORDS)