Characterization of interactions between bile salts and drugs by micellar electrokinetic capillary chromatography. Part I

PURPOSE: The general properties of micellar electrokinetic capillary chromatography (MECC) were utilized to characterize the strength of interactions between bile salts and biological active substances. METHODS: For that purpose various bile salts were used as micellar pseudostationary phase in the background electrolyte. Furthermore, a physicochemical model was applied and the effective partition coefficients between micellar and water phase were calculated in order to evaluate the strength of interactions between bile acids and the drugs. RESULTS: It was found that the interactions between the selected drugs and bile salts depend both on the lipohilicity of the drugs and on the charge of the components. Only hydrophobic, cationic drugs such as quinine and propranolol are able to interact with these surface active agents. CONCLUSIONS: MECC is a valuable method to characterize interactions such occurring between drugs and bile salts.     

Application of capillary electrophoresis of characterizing interactions between drugs and bile salts. Part I

Capillary electrophoresis offers a new way of characterizing interactions between different bile salts and drugs. The observed interactions were characterized with modified model functions known from affinity capillary electrophoresis (ACE) an micellar electrokinetic capillary electrophoresis (MECC). The methodical background of both methods is the change of the ionic mobility of the drug caused by partition between phases and aggregation with the bile salt molecules, respectively. This phenomenon is described by two different physicochemical models. A parameter estimation was carried out in order to obtain the partition coefficients KP as well as constants for the aggregate formation KA. Furthermore, an expression about the specific molar volume of the micelles and stoichiometric coefficients can be given.     

Effect of various lipid-bile salt mixed micelles on the intestinal absorption of amphotericin-B in rat

We investigated the effect of the somatosensory functions to the outcomes of motor functions in 28 patients with thalamic hemorrhage. The disturbance of the pyramidal tracts was assessed by the destruction of the internal capsule found in computed tomography (CT). The disturbance of the somatosensory function was analyzed by the N20 component of short-latency somatosensory evoked potentials (SSEP). The outcomes of motor function was evaluated after 3 months of ictus. Correlations between the outcomes of motor function, disturbance of the pyramidal tract, and disturbance of the somatosensory function were discussed. The result indicated that functional outcomes statistically correlated with neither disturbance of the internal capsule alone nor disturbance of N20 alone. But, there was statistically significant between functional outcomes and the combination of disturbance of the internal capsule with disturbance of N20 (p < 0.05, Wilcoxon signed-rank). There was not statistical difference in hematoma volume or consciousness. The implications of these results suggest that somatosensory function may affect the recovery of motor functions.     

Mechanism of biochemical action of substituted 4-methylbenzopyran-2-ones. Part 3: A novel mechanism for the inhibition of biological membrane lipid peroxidation by dioxygenated 4-methylcoumarins mediated by the formation of a stable ADP-Fe-inhibitor mixed ligand complex

7,8-Dihydroxy-4-methylcoumarin (DHMC) and 7,8-diacetoxy-4-methylcoumarin (DAMC) have been reported to effectively inhibit in-vivo lipid peroxidation in rat tissues induced by CCl4 and paraquat. DHMC was found to readily impart green colour to the lipid peroxidation incubation mixture containing ADP and Fe3+, whereas DAMC formed green complex only upon incubation with liver microsomes, confirming our earlier observation that liver microsomal deacetylase hydrolyses DAMC to DHMC. Sensitive pH metric technique revealed the formation of ADP-Fe-DHMC ternary complex with highest stability, while Fe-DHMC and ADP-DHMC had negligible stabilities concluding that ADP-perferryl ion formation is prevented by DHMC resulting in the production of stable ternary mixed ligand complex (ADP-Fe-DHMC), thereby inhibiting the formation of O2-, and eventually other reactive oxygen species (ROS) responsible for membrane lipid peroxidation.