ABSTRACT
Preparation Methadoxine is equimolar salt, which cationic component (pyridoxine) is 3-oxypyridine derivative, possessing B6-vitamine like activity, while anionic component is the cyclic lactame of glutamic acid. Since biopharmaceutical and pharmacological properties of this drug depend on biochemical transformation its components, of the aim of this work was to determine the structure of possible ionized pyridoxine and pyrrolidone carboxylate forms and their reaction ability in biochemical processes. Physical-chemical properties of compounds (pKa, logP, logD, proton donor/acceptor quantity, solubility (g/l)) were calculated with ACD/pKaDB program or obtained from Pub-Med physical/chemical properties database. UV spectra of compounds were obtained after dissolution in different pH solutions (1.0, 4.5 and 6.8). It was found that at different pH values one can observe changes of the absorption spectra due to the presence of prevailing amount of the protonated form. An analysis of both pKa, logP and logD indicators and reactive functional groups of Methadoxine components has revealed that they can be protonated in different regions of gastro-intestinal tract, that influences their solubility in hydrophilic and lypophilic media. Pharmacological properties of pyridoxine and pyrrolidone carboxylate themselves are performed after their preliminary biotransformation to active metabolites. Only ionic interaction between Methadoxine components in the substance composition can appear, that provides its pharmaceutical stability and ensures its activity only in the organism conditions.
Subject(s)
Glutamic Acid/chemistry , Lactams, Macrocyclic/chemistry , Protons , Pyridoxine/chemistry , Pyrrolidonecarboxylic Acid/chemistry , Drug Stability , Hydrogen-Ion Concentration , Hydrophobic and Hydrophilic Interactions , Solubility , Solutions , Spectrophotometry, Ultraviolet , Water/chemistryABSTRACT
Pharmacokinetics of amixin was studied after repeated administration (5 days) to animals. Perorally administered amixin is characterized by high bioavailability and is present in the circulation in high concentrations for a long time. The main pharmacokinetic parameters were estimated by the method of linear regression because of slow elimination of amixin from organs and tissues. Our results indicate that repeated treatment with amixin holds much promise for the prevention and therapy of chronic diseases (particularly hepatitides).
Subject(s)
Tilorone/pharmacokinetics , Administration, Oral , Animals , Area Under Curve , Hepatitis/drug therapy , Kinetics , Linear Models , Male , Mice , Tilorone/administration & dosage , Tilorone/pharmacology , Time Factors , Tissue DistributionABSTRACT
We studied the effect of lauric acid on transdermal penetration of phenazepam in vivo. It was found that treatment with lauric acid 3-fold increased the maximum anticonvulsive effect of phenazepam applied in a transdermal therapeutic system in comparison with the control. Study of the pharmacokinetics of phenazepam transdermal therapeutic system showed its higher bioavailability in the presence of lauric acid (f=0.9).
Subject(s)
Anticonvulsants/pharmacokinetics , Benzodiazepines/pharmacokinetics , Lauric Acids/pharmacokinetics , Skin/drug effects , Administration, Cutaneous , Animals , Anticonvulsants/administration & dosage , Anticonvulsants/blood , Area Under Curve , Benzodiazepines/administration & dosage , Benzodiazepines/blood , Biological Availability , Brain/metabolism , Drug Synergism , Hydrogels/pharmacokinetics , Lauric Acids/pharmacology , Mice , Permeability , Skin/metabolismABSTRACT
The kinetics of labeled 3-hydroxyphenazepam (active phenazepam metabolite) after its intravenous and transdermal administration was studied. Biphasic kinetic of drug distribution in the organism was revealed; pharmacokinetic parameters and biological availability (1.32 0.12 for the plasma and 1.21 0.10 for the brain) were determined on the basis of total radioactivity of the plasma and brain.
