In-vitro relationship between protein-binding and free drug concentrations of a water-soluble selective beta-adrenoreceptor antagonist (atenolol) and its interaction with arsenic

Abstract

The degree of binding of a drug to plasma proteins has a marked effect on its distribution, elimination, and pharmacological effect since only the unbound fraction is available for distribution into extra-vascular space. The protein-binding of atenolol was measured by equilibrium dialysis in the bovine serum albumin (BSA). Free atenolol concentration was increased due to addition of arsenic which reduced the binding of the compounds to BSA. During concurrent administration, arsenic displaced atenolol from its high-affinity binding Site I, and free concentration of atenolol increased from 4.286 +/- 0.629% and 5.953 +/- 0.605% to 82.153 +/- 1.924% and 85.486 +/- 1.158% in absence and presence of Site I probe respectively. Thus, it can be suggested that arsenic displaced atenolol from its binding site resulting in an increase of the free atenolol concentration in plasma.

Fig. 1.

Free concentration of warfarin and diazepam bound to BSA upon the addition to atenolol at pH 7.4 and 27 °C

Fig. 2.

Free concentration of atenolol when used with warfarin and diazepam bound to BSA at pH 7.4 and at temperature of 27 °C

Fig. 3.

Free concentration of atenolol bound to BSA upon the addition of arsenic trioxide in absence and presence of Site I-specific probe

Fig. 4.

Proposed models of the atenolol-BSA-arsenic interaction in absence and presence of warfarin (Site I-specific probe)