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Concentration-dependence of disopyramide binding to plasma protein and its influence on kinetics and dynamics.

Disopyramide binds to two independent sites on protein in human plasma. The first binding site located on alpha-1-acid glycoprotein has an association and a capacity constant of 1.0 x 10(6) M-1 and 3.5 x 10(-6) M, respectively, and accounts for the majority of disopyramide binding. The second site is probably located on albumin and accounts for 5 to 10% of the binding. The bound fraction of disopyramide was concentration-dependent at drug concentrations reported to be therapeutic. After administration of 100, 150, 200 and 300 mg doses of disopyramide (Norpace) to each of four human volunteers, the area under the free (unbound) disopyramide serum-concentration time curve averaged 2.32, 3.33, 5.21 and 8.24 mg/l. hr, respectively, and was directly proportional to dose. The elimination half-lives based on free and total drug concentrations averaged 4.36 and 6.51 hr, respectively (P less than .001), and were dose-independent. The peak response (change in pre-ejection period) and area under the response time curves were better related to free than to total serum concentrations of disopyramide.[1]

References

  1. Concentration-dependence of disopyramide binding to plasma protein and its influence on kinetics and dynamics. Lima, J.J., Boudoulas, H., Blanford, M. J. Pharmacol. Exp. Ther. (1981) [Pubmed]
 
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