Effect of sodium salts of 3α,12α-dihydroxy-7-oxo-5β-cholanoic and 3,7,12-trioxo-5β-cholanoic acids on verapamil hydrochloride in biophysical-chemical model experiments

Abstract

It is known that certain bile acids have a promotive effect on the action of some drugs. Special attention is paid to bile acids having oxo groups instead of OH groups in the steroid skeleton of their molecule, since these derivatives have a lower hemolytic potential (membrane toxicity). This study examined the effects of sodium salts of 3α,12α-dihydroxy-7-oxo-5β-cholanoic acid (7-oC) and 3,7,12-trioxo-5β-cholanoic acid (3,7,12-toC) on the adsorption of verapamil hydrochloride on activated carbon (model of the cell membrane). The interaction was followed by measuring the effect of verapamil on the functional dependence between the spin-lattice relaxation time T 1 (protons of the C18 angular group of the bile acid molecule) and the bile acid concentration in deuterated chloroform (model of the cell membrane lipid phase). Whether a depot effect of verapamil exists when 7-oC and 3,7,12-toC (in the form of methyl esters) are present in chloroform was also investigated. It was found that 7-oC exhibited a significant effect in the experiments with verapamil, whereas 3,7,12-toC showed no difference of the measured parameters with respect to the control. This indicates that bile acid molecules should have OH groups bound to the steroid nucleus, in order to exhibit an effect on the monitored physico-chemical parameters of verapamil.