Dynamic variability of binding of antiarrhythmic drugs during the evolution of acute myocardial infarction

K. M. Kessler, B. Kissane, J. Cassidy, K. C. Pefkaros, P. Kozlovskis, C. Hamburg, R. J. Myerburg

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

We tested the hypothesis that the hnanges in free fatty acid and α1-glycoprotein concentrations, which occur during acute myocardial infarction, exert asynchronous and opposing influences on the serum protein bonding of selected drugs. Free drug fractions of two antiarrhythmic agents with contrasting binding characteristics, quinidine and procainamide, were related to free fatty acid and α1-glycoprotein concentrations on days 1 through 5 and 10 in 20 patients with acute myocardial infarction. The mean free quinidine fraction was elevated on day 1 (9.0 ± 4.4% vs 6.7 ± 2.7% in patients with stable heart disease; p < .05) and fell progressively to day 10 (4.0 ± 2.8%; p < .0002) as free fatty acid concentration decreased (day 1 = 464 ± 272 meq/liter; day 10 = 264 ± 155 meq/liter; p < .01) and α1-glycoprotein concentration increased (day 1 = 98 ± 31 mg/dl; day 10 = 141 ± 47 mg/dl; p < .02). Multiple stepwise regression showed a major influence of changing α1-glycoprotein concentration on the observed sequential changes in the free quinidine fraction (p < .005). In contrast, no serial changes in procainamide binding were noted. In conclusion, metabolic changes during the course of acute myocardial infarction sequentially alter free quinidine fraction and, consequently, may influence pharmacodynamics.

Original languageEnglish (US)
Pages (from-to)472-478
Number of pages7
JournalCirculation
Volume70
Issue number3 I
DOIs
StatePublished - Jan 1 1984
Externally publishedYes

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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    Kessler, K. M., Kissane, B., Cassidy, J., Pefkaros, K. C., Kozlovskis, P., Hamburg, C., & Myerburg, R. J. (1984). Dynamic variability of binding of antiarrhythmic drugs during the evolution of acute myocardial infarction. Circulation, 70(3 I), 472-478. https://doi.org/10.1161/01.CIR.70.3.472