Protein binding interaction of warfarin and acetaminophen in presence of arsenic and of the biological system

Abstract

Equilibrium dialysis was used to study in vitro binding of acetaminophen at physiological pH and temperature in Bovine serum albumin (BSA). The binding of acetaminophen and warfarin mixture was studied to determine the effect of acetaminophen on the other's (warfarin) interaction with the protein in presence of arsenic. The free fractions were determined by UV spectrophotometric technique. The binding of warfarin to bovine serum albumin depended on both drug and arsenic concentrations. Free warfarin concentration increased due to addition of acetaminophen which reduced the binding of warfarin to BSA. Free warfarin concentration also increased accordingly by increasing the concentration of acetaminophen when only the BSA was present. When the binding site was blocked by sufficient amount of arsenic the increment of free concentration of warfarin decreased to a lower extent. Thus free concentration of warfarin increased from 3.19±0.64% and 0.83±0.09% to 86.82±0.53 and 75.82±4.91% in absence and presence of site-II probe (arsenic) respectively when acetaminophen added with an increasing concentration from 10 mcM to 80 mcM. This suggests that in the presence of arsenic the warfarin being slowly displaced from its high affinity binding site with increasing acetaminophen concentration.