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KMID : 0369819850150010001
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Jorunal of Korean Pharmaceutical Sciences
1985 Volume.15 No. 1 p.1 ~ p.7
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Protein Binding of Disopyramide. Displacement by Mono -N-Dealkyl Disopyramide and Variation with Commerical Source of Alpha-1-Acid Glycoprotein
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David B. Haugh ey
Irving Steinberg and 이민화
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Abstract
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Previous studies show that the free (unbound) fraction of disopyramide in human serum is drug concentration dependent~ at corresponding serum disopyramide concentrations that are achieved clinically. Moreover, disopyramide free fraction values vary several fold at any given drug concentration in human serum and tend to decrease as serum cocentrations of alpha-I-acid glycoprotein(AAG) incrase. A recent study demonstrates that the free fraction of disopyramide inhuman serum increases almost 2-fold following the addition of 14.4μM/L mono-N-dealkyldisopyramide. These studies and others. 6),7) prompted the present investigation to characterize the protein binding of disopyramide in human serum and solutions of AAG in the presence of mono-N-dealkyldisopyramide (a major metabolite of, disopyramide) and to determine the utility of using commercially available alpha-I-acid glycoprotein for drug protein binding displacement studies. Because many basic and acidic compounds are known to bind to alpha-I-acid glycoprotein 8) the present study. was performed to determine whteher commercially available AAG would provide a convenient protein source for such binding studies.
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