Work is devoted to a comparative analysis of the pharmacological action and integral indicators pharmacokinetics of 1,4- benzodiazepine - phenazepam and levan, as well as their total active 3-oximetabolite formed by different mechanisms. It is shown that in the tests levan antagonism corazolum and thiosemicarbazide inferior phenazepam anticonvulsant activity, but surpasses phenazepam on activity in the maximal electroshock test and has a lower severity miorelaxation action. Comparison effects of phenazepam and levad with effects of 3-oximetabolite indicate greater similarity effects than metabolite with phenazepam. With the use of radiolabeled compounds were established change in the ratio of the areas under the concentration curve 3-oximetabolite in the brain and blood when administered phenazepam (AUC brain / AUC blood = 0,96 ± 0,27) or levan (AUC brain / AUC blood = 1,4 ± 0,1). This fact is associated with different ways of biotransformation: oxidative hydroxylation of phenazepam CYP450 and nonspecific carboxylesterase hydrolysis of levan, which explains the difference in the pharmacological effect of the test compounds.

The pharmacodynamics and pharmacokinetics of hemisuccinate 3-hydroxyphenazepam (HS-3-HPh, levana)--a new hypnotic 1,4-benzodiazepine derivative--have been studied. It is established that HS-3-HPh in doses of 0.05, 0.1 and 2 mg/kg produces reliable hypnotic action (shortens the period of falling asleep, reduces the number of awakenings at night-time, and increases sleep duration) in the hexenal sleep potentiation test on mice. After a 7-day drug administration, no withdrawal syndrome has been observed. The concentration of 3-oxyphenazepam (3-OP, the main metabolite of HS-3-HPh) in brain after drug administration is significantly higher than the content of 3-OP upon its introduction. The content of 3-OP upon its introduction rapidly decreases, while that upon the administration of HS-3-HPh is retained on a stationary level for a rather long time (about 6 h). It can be suggested that a specific character of HS-3-HPh hypnotic action is determined by peculiarities of its pharmacokinetics, namely, easier entering the brain and subsequent hydrolysis with release of the active metabolite (3-OP).

The pharmacodynamics and pharmacokinetics of hemisuccinate 3-hydroxyphenazepam (HS-3-HPh, levana) - a new hypnotic 1,4-benzodiazepine derivative - have been studied. It is established that HS-3-HPh in doses of 0.05, 0.1 and 2 mg/kg produces reliable hypnotic action (shortens the period of falling asleep, reduces the number of awakenings at night-time, and increases sleep duration) in the hexenal sleep potentiation test on mice. After a 7-day drug administration, no withdrawal syndrome has been observed. The concentration of 3-oxyphenazepam (3-OP, the main metabolite of HS-3-HPh) in brain after drug administration is significantly higher than the content of 3-OP upon its introduction. The content of 3-OP upon its introduction rapidly decreases, while that upon the administration of HS-3-HPh is retained on a stationary level for a rather long time (about 6 h). It can be suggested that a specific character of HS-3-HPh hypnotic action is determined by peculiarities of its pharmacokinetics, namely, easier entering the brain and subsequent hydrolysis with release of the active metabolite (3-OP).

Biopharmaceutical classification system (BCS) is based on solubility tests; for various drugs they correlate with their bioavailability in human body. It is widely used in design and development of innovation drugs, new dosage forms (permeability amplifiers), in clinical pharmacology (drug-drug, drug-food interaction) and also by regulation agencies of several countries as the scientific approach, for testing of waiver on bioavailability.Review considers modern concepts and theoretical bases for prediction of bioavailability according to BCS. It gives characteristics of fundamental parameters of the system: absorption number, solubility number and the ratio of dose to the soluble part of the drug. Possible versions of BCS modification for its subsequent optimization are discussed.

Biopharmaceutical classification system (BCS) is based on solubility tests; for various drugs they correlate with their bioavailability in human body. It is widely used in design and development of innovation drugs, new dosage forms (permeability amplifiers), in clinical pharmacology (drug-drug, drug-food interaction) and also by regulation agencies of several countries as the scientific approach, for testing of waiver on bioavailability. Review considers modern concepts and theoretical bases for prediction of bioavailability according to BCS. It gives characteristics of fundamental parameters of the system: absorption number, solubility number and the ratio of dose to the soluble part of the drug. Possible versions of BCS modification for its subsequent optimization are discussed.

The kinetics of excretion of 2-(14)C-3-hydroxyphenazepam and its metabolites were studied upon a single transdermal and intravenous administration in mice. The main fraction of the total radioactivity (approximately 80%) was eliminated within approximately 84 h upon intravenous injection and within approximately 360 h after transdermal introduction. In the latter case, the ratio of lipophilic and hydrophilic metabolites is modified as well: the former fraction increases by a factor of 1.75, while the latter decreases by a factor of 1.2 as compared to the case of intravenous drug administration.

Antiviral and interferon inducing activity of the amixine and its some derivatives, as well as their influence on the proteolytic enzymes activity, monooxygenase activity of the microsomal fraction, level of the lipids peroxidation were studied. Lack of correlation between antiviral and interferon inducing activity in the investigated series of compounds was found. Vice versa, the good correlation between interferon inducing activity and the elastase-like activities inhibition ability of the compounds was observed. It allows to state the assumption, that only one ability of compounds to induce of an interferon doesn't suffice for obtaining of high titres of interferon, and while their rather high antiproteolitic activity is necessary. It's shown, that except for one compound the influence of amixine and its derivatives on the red-ox enzymes activity well correlates with their ability to the interferon-inducing. All presented above allows to attribute amixine and its derivatives to polymodal antiviral agents.

It has been studied how preventive administration of EDTA influences toxic NO2- induced pulmonary edema and disturbances in antioxidant systems. The compound in question, being preventively administered, has exerted a significant antiedematic effect as a result of a decrease in lipid peroxidation intensity and protection of the most important substrate components of the nonenzymatic antioxidant system from the oxidation effect.

Effect of preliminary intraperitoneal injection on the state of the glutathione system and lipid peroxidation intensity in the lungs of rats subjected to NO2 has been studient. This compound is shown to decrease significantly all lipid peroxidation processes and to inhibit completely glutathion oxidation. These effects are supposed to be a result not only of antioxidant properties of enomelanin, but also of its ability to promote a decrease in the activity of glutathione-depending enzymes subjected to NO2.

Prophylactic injection of enomelanine has been studied for its effect on hemic hypoxia and on different parts of breathing system. The enomelanine was shown to be effective for decreasing the level of carboxyhemoglobin and for protection from succinate dehydrogenase and cytochromoxidase. The authors think that these effects of enomelanine are conditioned not only by its anti-hypoxia abilities, but also by the capacity to activate the alternative protective mechanisms of the cell.

Influence of intraperitoneal administration of polygalacturonic acid derivatives at a dose of 100 mg/kg on the glutathione system and lipid peroxidation in the rat lung after treatment with NO2 was studied. A considerable decrease of lipid peroxidation intensity by these derivatives was caused not only by ability of these compounds to the chelate formation and absorption of free radicals, but also by the substantial activation of the glutathione system.

Natural porphyrin (hemin and its synthetic analogue--tetraphenylporphyrin with iron TPP-Fe3+) has been studied for its effect on activity of monooxygenase responses and cytochrome P-450 content against a background of introduction of four-chlorine carbon in the in vitro experiments. The reducing effect of hemin and TPP-Fe3+ on cytochrome P-450 and dependent enzymes: N-demethylase, n-hydroxylase and benz(a)pyrene hydroxylase has been noticed; the synthetic analogue of heme was more efficient.

Pharmacodynamics and pharmacokinetics of a novel tranquilizing agent--gidazepam (I), a prodrug, and its physiologically active metabolite--7-bromo-5-phenyl-1,2-di-hydro-3H-1,4- benzodiazepine-2-one (II) in mice organism were studied. The form of relationship was determined between the dynamics of the anticonvulsant effect of labelled (2-14C-) I and II and the kinetics of the content of 14C-compounds in the experimental animals brain. It was noted that the biophase of the effect and the effector fragment of the scheme of biokinetics for I and II are identical. The effector prognosis of pharmacokinetics of I was realized. The comparison of the main characteristics of biokinetics for the prodrug (I) and drug (II) allowed us to reveal the nature of the quantitative differences of these pharmacological effects.