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. 3450091-150X/05/3907-0345

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.

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-(b-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.Tetramezine, or N,N¢-ethylene-bis(3,3-dimethyldiaziridine), is a new biologically active compound possessing a pronounced antidepressant activity [1]. Previously, we have developed a convenient chromatographic method for the quantitative determination of tetramezine in biological fluids and studied the experimental pharmacokinetics of this drug in rats [2]. The aim of this study was to elucidate the path-ways of tetramezine metabolism upon peroral and intramuscular administration in rats. EXPERIMENTAL PARTThe experiments were performed on male mongrel rats weighing 200 ± 20 g, to which tetramezine was administered perorally (p.o.) and intramuscularly (i.m.) in doses of 200 and 500 mg/kg (which corresponded to pharmacologically active amounts of 13.8 and 34.5% of the half-lethal dose), re-7 0091-150X/07/4101-0007

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).

The work investigated the effect of UV and microwave radiation on the spectral characteristics of aqueous solutions of nitrofural. For this, aqueous solutions of the drug were irradiated, and the spectra were compared before and after exposure.