ISSN:
1432-1041
Keywords:
gallopamil
;
plasma protein binding
;
alpha-1 acid glycoprotein
Source:
Springer Online Journal Archives 1860-2000
Topics:
Chemistry and Pharmacology
,
Medicine
Notes:
Summary We have determined the extent and variability in the binding of gallopamil to human serum proteins. Binding was determined by equilibrium dialysis in healthy volunteer serum, human serum albumin (45 g·l−1), and alpha-1 acid glycoprotein (AAG) (600 mg·l−1) at a pH of 7.4. Nonlinear regression analysis of gallopamil binding over a wide range of concentrations (10−9 to 10−4 M) in healthy volunteer serum suggested two classes of binding sites (kass.1=4.7×105M−1, kass.2=4.1×104M−1). These values were in close agreement with those obtained from binding to AAG and human serum albumin. Gallopamil free fraction over the concentration range of 10 to 100 ng·ml−1 was independent of concentration. The free fraction in 20 volunteers was 0.075 at a concentration of 10 ng·ml−1. Gallopamil free fractions were also determined in human serum albumin, to which various concentrations of AAG were added. Bound/free ratios correlated with AAG. As we changed the pH of the serum from 7.0 to 8.0, the free fraction changed from 0.1 to 0.05. Verapamil, lignocaine, procainamide, propranolol, 40H-propranolol, MEGX, and NAPA all caused an increase in the free fraction of gallopamil in serum. However, tocanide, quinidine, diltiazem, GX, norverapamil, D620, D617, and desacetyl diltiazem had no effect on gallopamil binding. Therefore, the data strongly suggest AAG as the high affinity, low capacity binding site and albumin as the low affinity, high capacity binding site for gallopamil, variability in gallopamil binding can be explained by alterations in AAG concentrations, pH, and the presence of other drugs and their metabolites.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF00637633
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