[Proxodolol pharmacokinetics in rats and rabbits]. / Farmakokinetika proksodolola u krys i krolikov.

In non-inbred rats, the pharmacokinetics of proxodolol was studied after its intravenous administration in a dose of 1 mg/kg or oral use in a dose of 50 mg/kg as 1% aqueous solution, in Chinchilla rabbits, it was examined after intravenous administration in a dose of 1 mg/kg as 1% aqueous solution and oral use in a dose of 40-50 mg/kg as 40-mg tablets. The equilibrium dialysis method was applied to explore proxodolol binding to human and rat serum proteins in vitro. Proxodolol was demonstrated to be slightly distributed in the rat peripheral tissues and more actively in the rabbits (the stationary distribution volume was 0.264 and 2.27 1/kg, respectively). After intravenous injection, the total proxodolol clearance in the rats and the rabbits was 0.229 and 2.24 1/h/kg, the area beneath the concentration-time curve was 5702 and 964 ng/h/ml, the terminal half-life was 1.44 and 1.49 h, the mean retention time was 1.16 and 1.52 h, respectively. The pattern of rabbit serum proxodolol concentration curves after intravenous infusion suggests that the drug shows enterohepatic recirculation. After oral administration, the drug was rapidly absorbed from the gastrointestinal tract; the maximum concentration time was 0.58 h in rats and 0.70 h in rabbits. The mean absorption time was 0.77 and 0.64 h in rats and in rabbits, respectively. The absolute proxodolol bioavailability was determined to be 3.51 and 3.02% in rats and in rabbits, respectively. The in vitro serum protein-binding of proxodolol was 34% in rats and 66% in man.

[Distribution of prazosin and its metabolites in animal organs during chronic administration]. / Raspredelenie prazozina i ego metabolitov v organakh zhivotnykh pri khronicheskom vvedenii.

The distribution of prazosin and its metabolites in organs of rabbits and rats during oral long-term administration at different doses was studied. Prazosin was shown to be accumulated in the animals' organs. Three metabolites of prazosin one of which was identified were detected in the blood serum, bile and organs of the animals. The contents of prazosin and the metabolites in organs and tissues were non-linearly related to the dose.

[Slow elimination of a prazosin metabolite compared to prazosin kinetics after its intravenous administration to rabbits]. / Zamedlennaia éliminatsiia metabolita prazozina v sravnenii s kinetikoi prazozina posle vnutrivennogo vvedeniia krolikam.

Serum concentration profiles of prazosin and its metabolite 2-(1-piperazinyl)-4-amine-6,7-dimethoxyquinazoline after intravenous bolus administration to rabbits (0.5 mg/kg) were shown to be biphasic. Rapid decline related to distribution was followed by a terminal slope lasting for up to 24 hours. Prazosin level in this phase decreased, its elimination half-life being about 9 hours, while the metabolite serum level was almost constant between 4 and 24 hours and averaged 0.9 mumol/l. This is in keeping with the earlier suggested extremely low elimination rate of this metabolite. Enterohepatic recirculation may account for this phenomenon, as well as a significant rise in the metabolite serum concentration I hour after the injection.

[Effect of cefuroxime on embryonic and fetal development in an experiment]. / Vliianie tsefuroksima na razvitie émbriona i ploda v éksperimente.

The direct and indirect effects of cefuroxime on the embryo and fetus were studied in vitro and in vivo at different gestation times. The placenta, liver and kidneys of the mother and fetus were investigated morphologically. It was shown that in a dose of 250 mg/kg the antibiotic did not induce disorders in the fetus development. The histological examination of the fetus placenta and liver revealed no changes as compared to the controls. However, in the renal tubules of the mother and fetus, pathological lesions in the form of the cytoplasm granular degeneration and nucleus swelling, lysis and necrosis were observed. These lesions were of a dose-dependent character. The possible nephrotoxic effect of cefuroxime prevents its use as a drug of choice in treatment of gestation pyelonephritis.

[Evaluation of the effect of the antihistaminic preparations dimebon and diprazin on embryogenesis in rats]. / Otsenka vliianiia antigistaminnykh preparatov dimebona i diprazina na émbriogenez krys.

A single administration of dimebon (800 mg/kg) to rats per os (2/3 of the LD50 isoeffective for females) raises the preimplantation death, whereas pipolphen increases the intrauterine lethality and inhibits the development of fetuses. Pipolphen in a dose of 175 mg/kg and dimebon in doses of 300-150 mg/kg (exceeding 25- and 300-150-fold, respectively, the therapeutic dose for man) do not exert any specific embryotropic action.

[Tolerance for nonsteroidal anti-inflammatory agents by experimental animals during pregnancy]. / Perenosimost' nekotorykh nesteroidnykh protivovospalitel'nykh sredstv éksperimental'nymi zhivotnymi pri beremennosti.

The authors studied the tolerance of three nonsteroidal anti-inflammatory drugs, voltaren, indomethacin and ibuprofen by rats at different times of pregnancy and compared voltaren tolerance by pregnant and nonpregnant females. It was shown that as compared to nonpregnant animals, pregnant animals tolerated voltaren more poorly. The tolerance of both voltaren and indomethacin was particularly poor in the last trimester of pregnancy. The enhancement of the drug toxicity during pregnancy because of the changes in body function is discussed.

[Implantation and deciduation process after the action of the antihistamine preparation diprazin in early rat embryogenesis]. / Izuchenie protsessa implantatsii i detsiduolizatsii posle deistviia antigistaminnogo preparata diprazina v rannem émbriogeneze krys.

A histological and historadioautographical analysis of the uterine endometrium decidual tissue on the 5th, 6th, 7th and 8th days of pregnancy has shown that diprasin affects the processes of proliferation and differentiation of decidual cells, thus delaying the embryo's implantation. Deviations in the zonal division of decidual cells by their mitotic activity were found at all stages studied. The second (from the embryo) zone and mesometral part of deciduoma which are cambial regions proved to be the most sensitive. The data obtained suggest that the delay in embryonic development after the effect of diprasin is due to serious changes in deciduolization of endometrium.

[Pharmacokinetics of the new Soviet, tritium-labelled, antihistamine preparation, phencarol]. / Farmakokinetika novogo otechestvennogo protivogistaminnogo preparata fenkarola, mechennogo tritiem.

As evidenced no less than 45 per cent of tritium-labelled antihistaminic drug phencarol (quinuclidine-3-diphenylcarbinol hydrochloride) introduced intragastrically to rats is absorbed. The maximal radioactivity in various organs is reached in 1--3 hours, with high specific radioactivity being recorded in the lungs and liver and low--in the brain. The drug or radioactive products of its tranformation are eliminated largely via the gastrointestinal tract and kidneys.

[Rat placental barrier permeability for the new antihistaminic preparation, fenkarol]. / Issledovanie pronitsaemosti platsentarnogo bar'era krys dlia novogo protivogistaminnogo preparata fenkarola.

As established, following a single introduction of phencarol tagged with tritium in a quinuclidine nucleus perorally to rats on the 13th day of gestation its insignificant amounts gain access to the fetus through the placenta. The maximum concentration of the drug in the maternal blood was recorded 3 hours after its introduction, following 6 hours--in the placenta, with the radioactivity continuing to be constant during the first 6 hours in the embryonal tissues. In 48 hours after introduction the radioactive tag is still demonstrable in the study tissues. It is concluded that the drug is largely retained in the placenta, when introduced on the 13th day of pregnancy; on the 21st day of gestation the barrier functions of the placenta declines. The presence of phencarol and its transformation products in the embryonal tissues is confirmed by the method of thin-layer chromotography.

[Determination of embryotoxic and teratogenic effect of a new antidepressive agent, pyrazidol]. / Opredelenie embriotoksicheskogo i teratogennogo deistviia novogo antidepressanta pirazidola.

The effect of the new original antidepressant pyrasidol on the embryogenesis of albino rats was investigated. With a single introduction of the drug with a tube into the stomach in a dose of 200 mg/kg within the first 15 days of pregnancy pyradisol was found to produce no embrytoxic and teratogenic effects. Fluorescent microscopy revealed the presence of the pyrasidol metabolites in the amniotic fluid of the test animals 2 hours after enteral administration of the drug, on the 15th and 20th days of pregnancy.