Mashiur Rahman
1, Farzana Prianka
1, Mohammad Shohel
2, Md. Abdul Mazid
1*1 Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Dhaka, Dhaka-1000, Bangladesh.
2 Department of Pharmacy, North South University, Dhaka- 1229, Bangladesh.
Abstract
Purpose: The aim of this study was to
characterize the binding profile as well as to notify the interaction of
palmitic acid with metoprolol succinate at its binding site on albumin.
Methods: The binding of metoprolol
succinate to bovine serum albumin (BSA) was studied by equilibrium dialysis
method (ED) at 27°C and pH 7.4, in order to have an insight in the binding
chemistry of the drug to BSA in presence and absence of palmitic acid. The
study was carried out using ranitidine as site-1 and diazepam as site-2 specific
probe.
Results: Different analysis of binding of metoprolol succinate
to bovine serum albumin suggested two sets of association constants: high
affinity association constant (k1 = 11.0 x 105 M-1)
with low capacity (n1 = 2) and low affinity association (k2
= 4.0×105 M-1) constant with high capacity (n2
= 8) at pH 7.4 and 27°C. During concurrent administration of palmitic acid and
metoprolol succinate in presence or absence of ranitidine or diazepam, it was
found that palmitic acid displaced metoprolol succinate from its binding site
on BSA resulting reduced binding of metoprolol succinate to BSA. The increment
in free fraction of metoprolol succinate was from 26.27% to 55.08% upon the
addition of increased concentration of palmitic acid at a concentration of 0×10-5
M to 16×10-5 M. In presence of ranitidine and diazepam, palmitic
acid further increases the free fraction of metoprolol succinate from 33.05% to
66.95% and 40.68% to 72.88%, respectively.
Conclusion: This
data provided the evidence of interaction at higher concentration of palmitic
acid at the binding sites on BSA, which might change the pharmacokinetic
properties of metoprolol succinate.