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

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.

Effect of physicochemical parameters on skin permeability of antihypertensive.

Studies were carried out to establish a correlation of skin permeability with physicochemical parameters using five antihypertensive drugs. In vitro skin permeation was carried out in vertical type diffusion cells. When steady-state fluxes of the drugs were correlated with physicochemical properties, good correlation was obtained with the reciprocal of melting point. Weak correlation was obtained with partition coefficient, molecular weight and solubility. However skin permeability versus solubility profiles revealed an interesting trend. The initial permeation rates of the poorly water soluble drugs, prazosin hydrochloride and reserpine were higher than their steady-state fluxes and moderately water soluble drug atenolol showed more or less similar permeation throughout the entire span of the study. This trend changed gradually and reversed completely in the highly water soluble drug diltiazem hydrochloride. The study suggests that drug derivatives of low melting point and good aqueous solubility could be favorable candidates for transdermal delivery.