Abstract
Objective: A drug can replace other drugs in the same binding position in protein plasma, increasing pharmacological response due to the increasedfree drug concentration. Drug shifting is critical when a compound is tightly bound to a protein. For example, a binding fraction change, from 98% to94%, may increase the free fraction 3 times, from 2% to 6%. Knowing that there is an interaction between mefenamic acid and piroxicam on plasmaprotein, more specifically on human albumin, this study aimed to visualize the interaction between both drugs and human albumin in silico.Methods: This study used AutoDock4 as a molecular docking technique, obtaining binding visualizations, binding energies (ΔG), and inhibitionconstants (Ki) of both mefenamic acid-albumin and piroxicam-albumin bindings.Results: It is shown that the ΔG and Ki of both mefenamic acid and piroxicam are −5.47 kcal/mol (98.59 μM) and −7.46 kcal/mol (3.42 μM), respectively.Conclusions: The process of binding mefenamic acid to albumin can be substituted with piroxicam due to its higher ΔG and Ki values. It can bepredicted that this interaction will increase the free mefenamic acid concentration in blood plasma which, in turn, enhances the therapeutic effect.
Highlights
The pharmacological activity of a drug depends on its concentration in the receptor, which is directly related to the free drug concentration in plasma
It is shown that the ΔG and Ki of both mefenamic acid and piroxicam are −5.47 kcal/mol (98.59 μM) and −7.46 kcal/mol (3.42 μM), respectively
The process of binding mefenamic acid to albumin can be substituted with piroxicam due to its higher ΔG and Ki values
Summary
The pharmacological activity of a drug depends on its concentration in the receptor, which is directly related to the free drug concentration in plasma. Changes in the free drug concentration in plasma, due to a result of drug interactions, can be detected in vitro by a variety of protein binding determination methods. Measurements of total drug concentrations do not provide necessary information about the fraction of the free drug in plasma that is available for distribution, elimination, and pharmacodynamics action. Accurate measurement of the concentration of free drug in the plasma is very important in clinical supervision. Free drug concentration in plasma is affected by changes in drug–protein binding. A drug’s plasma protein binding is critical to its clinical pharmacokinetics and pharmacodynamics, which are described by drug–protein binding parameters including the number of types of binding sites, the number of binding sites, and the affinity or strength of drug–protein binding [1]
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