N. Ya. Golovenko

Pharmacokinetics of Amixin after Repeated Peroral Administration to Mice

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).

Effect of Lauric Acid on Transdermal Penetration of Phenazepam In Vivo

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).

The protective properties of synthetic porphyrin tin complexes in toxic hyperbilirubinemia

Tin complexes of meso-substituted synthetic porphyrins, namely Sn4+-meso-tetraphenyl- porphyrin (Sn-TPP) and Sn4+-meso-tetrakis(N-methyl-3-pyridyl)porphyrin tetratosylate (Sn-TMe-3-PyP), efficiently decrease the serum bilirubin level when injected subcutaneously at a dose of 100 μM kg−1 body weight into mice. These compounds are active during hyperbilirubinemia, induced by phenylhydrazine, hemin and tetrachloromethane, and also during autoimmune hemolytic anemia. In the latter case a decrease in serum bilirubin content was observed, as well as a decrease in the amount of blood reticulocytes which reflects a milder course of the disease. The Sn complexes under study induce, in vivo, cytochrome P-450, inhibit microsomal heme oxygenase and decrease the intensity of lipid peroxidation. At the same time, in vitro the hepatic and splenic heme oxygenase activity is blocked only when a 0.1 μM concentration of Sn-TMe-3-PyP or Sn-protoporphyrin IX is added to the incubation mixture. Sn-TPP does not affect the activity of this enzyme in vitro.

Character of correlation between the anticonvulsant action of phenazepam and its level in the mouse brain

: The effect of low doses of haloperidol was studied by means of screening and electrophysiological tests. In doses of 0.05--0.15 mg/Kg haloperidol exerts an activating effect which manifests in the elevation of motility, in the potentiation of the convulsant effect of bicuculline, EEG desynchronization and decrement of test response depression in the recovery cycle of the somatosensory primary response. The data obtained suggest that the activating effect of haloperidol is due to the weakening of inhibitory processes in the brain.

Pharmacokinetics of Ethanol in Mice with Different Alcohol Motivation

We studied the pharmacokinetics of 14C-ethanol administered in various doses and via different routes to CBA, C57Bl/6, and (CBA×C57Bl/6)F1 mice. Kinetic scheme of ethanol distribution included its elimination by enzymatic (80-90% C0) and exponential (10-20% C0) mechanisms. Ethanol pharmacokinetics did not depend on the administration route and mouse strain. The kinetic scheme of ethanol distribution in mice was characterized by a dose-dependent linear increase in alcohol concentration in the plasma and brain and nonlinear (parabolic) increase in the area under its pharmacokinetic curve in the test tissue.

Analysis of the structure of components of the convulsant action of metrazol in mice receiving sulazepam and its metabolites

The relationship between minimal effective doses of pseudoclonic and clonico-tonic convulsions (DPCC, DCTC) and also of tonic extension (DTE), evoked by intravenous injection of metrazol into mice and the effect of the anticonvulsant action of sulazepam and its metabolites (diazepam, desmethyldiazepam, and oxazepam) were investigated. All the compouds tested were shown to increase the values of the minimal effective doses based on recorded indices of the seizure, and anticonvulsant activity reached a maximum 15 min after injection of desmethyldiazepam, 15–30 min after injection of sulazepam and oxazepam, and 5–30 min after injection of diazepam. Clear correlation was established between the minimal effective doses of the recorded indices of the seizure in the animals of the control group and it continued after injection of the drugs. It is postulated that sulazepam and its metabolites increase the minimal effective doses of metrazol for the recorded effect but do not change the general pattern of the seizure and do not affect dispersion of the dose—effect curves of metrazol.

Biokinetics of transdermal therapeutic medicinal form of phenazepam.

We studied the rate of phenazepam absorption into the blood and its transport to the brain from a transdermal therapeutic system and bioavailability of the drug in this system. Hydrogel matrix consisting of polyvinyl alcohol and 1,2-propylene glycol was used for application. Transdermal application of 0.1–0.4 mg phenazepam in a dose of 14 mg/kg provided a stable level of this drug during application interval (1–48 h), while its bioavailability for blood plasma and brain was 0.63 and 0.2, respectively (determined for 0.4 mg phenazepam). The rate of drug penetration into the blood and brain was 46 and 60 ng/ml/h, respectively.

Pharmacokinetics of bromonordiazepam and its14C-analog in single and prolonged patterns of administration

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Benzo(a)pyrene hydroxylase activity of immunocompetent cells

A study was made of aryl hydrocarbon hydroxylase activity in immunocompetent cells of varying origin and in hepatocytes from CBA mice. The cells from intact animals may be arranged in the following way with regard to the activity of the enzyme: macrophages greater than hepatocytes much greater than thymocytes greater than splenocytes. The immunostimulants (tilorone and its analogs) altered benzo(a)pyrene hydroxylase activity depending on the cell type.

Kinetics of [14C]phenazepam excretion in albino rats after single and repeated injections of the drug

During the 5 days after intraperitoneal injection of [14C] phenazepam into albino rats, both intact animals and animals previously receiving phenazepam injections for 15 days, about 77% of the total radioactivity was excreted with the urine and feces. The excretion processes can be described by a first-order equation. The rate of total excretion of phenazepam was identical after single or repeated injections of the drug. Meanwhile, after a single injection of phenazepam into the animals, it was excreted mainly with the urine, whereas after repeated injections it was excreted mainly with the feces. The process of excretion of phenazepam with the urine after repeated injection is biexponential in character.