A. S. Berlyand

Experimental evaluation of bioavailability of tetramezine from tablets

The absolute bioavailability f of the new antipsychotic drug tetramezine from tablets with intestine-soluble shell upon peroral administration in dogs amounted to 65.4% and was significantly higher than upon administration in the form of an aqueous solution of the parent substance (f = 48.1%). Comparative data on the peroral administration of the aqueous solution of tetramezine in dogs and rats showed that the bioavailability of tetramezine in dogs (48.1%) was much higher than that in rats (10%). The higher bioavailability of tetramezine from tablets is due to the intestine-soluble shell, which prevents the premature biotransformation of the drug in the acid medium of the stomach.

Excretion of Albicar from the Rat Organism

Albicar, or 2,6-dimethyl-4,8-diethyl-2,4,6,8-tetraazabicyclo(3.3.0)octane-3,7-dione, belongs to the class of bicyclic bisureas and exhibits pronounced psychopharmacological activity [1]. An important stage in studying the pharmacokinetics of new drugs is analysis of the excretion of a parent substance from the organism of experimental animals. Such experiments reveal the main drug elimination pathways; sometimes, this noninvasive sampling method can provide data for the calculation of important parmacokinetic parameters. This work is aimed at studying the excretion of albicar from the rat organism and using the noninvasive sampling data for the calculation of parameters of the drug pharmacokinetics.

Tetramezine metabolism in rats

The metabolism of the novel antipsychotic drug tetramezine in rats was studied using a computer-aided gas chromatography-mass spectrometry system. After peroral and intramuscular administration in rat, the drug is eliminated from the organism in the form of two metabolites. One of these is unambiguously identified as 1-(β-aminoethyl)-3,3-dimethyldiaziridine; the structure of the other metabolite also has a diaziridine framework. A considerable proportion of tetramezine is eliminated in the unchanged form.

Experimental Pharmacokinetics of Tetramezine in Rats

The pharmacokinetics of the new psychotropic agent tetramezine in rats has been studied with the aid of gas chromatography. The drug concentration profiles in the blood, excreta, and urine have been determined. Upon peroral administration, tetramezine is rapidly absorbed from the gastrointenstinal tract, and the maximum drug concentration in the blood plasma is observed within 5 min. The pharmacokinetics of tetramezine upon intravascular and intramuscular injections are dose-dependent and linear within the dose range studied. The average half-elimination times are 0.42 h (i.v.); 0.32 h (i.m.); and 0.42 h (p.o.). The obtained data are important for the subsequent investigation of the drug bioaccessibility and metabolism and for establishing relationships between the drug behavior in vitro, in experiments on animals, and in clinics.

Adsorption capacity of hydroxyapatite for several amino acids and heavy metal ions

The adsorption capacity of hydroxyapatite for several amino acids and heavy metal ions was investigated. The quantitative characteristics and laws of adsorption were determined. Possible adsorption mechanisms were discussed.

Investigation of tetramezine excretion from rats

The excretion of the novel antipsychotic agent tetramezine in rats was investigated using gas chromatography. Upon a single intramuscular administration in a dose of 200 mg/kg, only 5.2% of the introduced drug was recovered in the unchanged form, which implies that feces and urine are not the major routes of tetramezine excretion. The results suggest that tetramezine is well absorbed and the major proportion of it is subject to biotransformation, so that metabolism is the principal mechanism of clearance. The renal clearance (0.15 liter/(h · kg)) and half-elimination time (0. 37 h) for tetramezine in rats are determined using the experimental pharmacokinetic parameters (elimination constant and distribution volume).

Investigation of the Metabolism of Albicar in Rats

The experiments were performed on male rats to which albicar was administered perorally in the form an 8% aqueous solution in a single dose of 500 mg kg. The products of the drug’s metabolism were determined in urine collected over a 48 h period of time from animals kept in special boxes. To extract the compounds for analysis, 2 ml of urine were mixed with 40 ml of chloroform in a 50-ml tube with a ground-glass stopper and treated in a shaker for 15 min. After extraction, the tubes were kept in a refrigerator at –15°C. The chloroform layer was separated from the frozen aqueous layer, quantitatively transferred into another tube, and concentrated in a rotor evaporator (IR-1 type) under vacuum (water-jet pump) to a final volume of about 2 ml. This residue was quantitatively transferred into a microtube and evaporated in a flow of nitrogen to a final volume of 20 – 50 l. The chloroform extracts were introduced into the evaporator of a Finnigan 3200F (USA) gas chromatograph – mass spectrometer system with automated data processing facility. Chromatographic separation of the sample components was effected in a 45-m-long capillary column with an inner diameter of 0.3 mm. The analyses were performed with SE-52 immobile liquid phase at a gas-carrier (helium) flow rate of 1.5 ml min. The column temperature program was as follows: 2 min at 150°C followed by heating to 290°C at a rate of 6°C min; the evaporator and pipeline temperature was 260°C. The analyzed sample volume was 0.6 l. Figure 1 shows a typical chromatogram of the chloroform extract of a rat urine sample taken and prepared as described above. The retention times of albicar and its metabo-

Determining impurity elements in hydroxyapatite by laser mass spectrometry

The method of standard-free laser mass spectrometry was used to determine the quantitative content of impurities”in a synthetic hydroxyapatite. It is established that the content of impurities, in particular, toxic elements such as As, Zn, Pb, and Cr, is very low in the synthesized product. This allows the synthetic hydroxyapatite to be used as a material for intrabone implanatation.

Sorption properties of the new natural enterosorbent Klimont

It is established that the new enterosorbent Klimont absorbs effectively toxic organic substances (phenol, aniline, benzene, urea) in addition to heavy-metal cations even if the concentrations of these toxicants are many times over their maximum permitted concentrations in water. The sorption capacity of Klimont is comparable with that of other zeolites used for the purification of potable water.

Studying phenozan acid metabolism in rabbits

The metabolism of a new antioxidant agent — phenozan acid — was studied in rabbits. The main directions of this process are (i) oxidation of benzene ring with the formation of 2,6-di-tert-butyl-p-benzoquinone and (ii) dehydration of the propionic acid fragment with the formation of 4-hydroxy-3,5-di-tert-butylphenylacrylic acid methyl ester. The structures of metabolites were established by computer-aided gas chromatography/ mass spectrometry and confirmed by direct synthesis.