Premium
Disopyramide protein binding in plasma from patients with nephrotic syndrome during the exacerbation and remission phases.
Author(s) -
Echizen H,
Saima S,
Ishizaki T
Publication year - 1987
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/j.1365-2125.1987.tb03162.x
Subject(s) - disopyramide , orosomucoid , free fraction , nephrotic syndrome , exacerbation , medicine , albumin , chemistry , endocrinology , serum albumin , proteinuria , glycoprotein , pharmacokinetics , biochemistry , kidney
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)