В статье представлены результаты изучения параметров фармакокинетики оригинального противотуберкулезного препарата тиозонид, капсулы 100 мг (ЗАО «Фарм-Синтез», Москва) при однократном приеме возрастающих доз различными группами здоровых добровольцев в рамках клинического исследования I фазы.
Zolmitriptan is a widely used antimigraine drug, belongs to the group of second-generation tryptans, has a pronounced central mechanism of action and high selectivity to serotonin receptors of 5HT1D- and 5HT1B-types. Zolmitriptan belongs to hazard class 3 according to GOST 12.1.007-76: DL50 are 660 (495 - 881) mg/kg for male mice and 1045 (749 - 1292) mg/kg for female mice when administered into the stomach. When injected into the abdominal cavity, DL50 is 172 (131 - 225) mg/kg for male mice. The drug has a weak irritating effect on the mucous membranes of the eyes, does not irritate the skin, there are no signs of skin-resorptive action, and has a low ability to accumulate. The threshold of acute inhalation action is set at 0,9 mg/m3 for the effect on the functional state of the nervous system and liver. For the zolmitriptan aerosol, it is recommended to approve the tentative safe exposure level in the air of the working area at 0,01 mg/m3 and the tentative safe exposure level in the atmospheric air of urban and rural settlements at 0,0001 mg/m3.
Quetiapine is a psychotropic drug, a dibenzothiazepine derivative and a representative of the class of neuroleptics (antipsychotic drugs) of a new subgroup – atypical antipsychotic drugs («second-generation antipsychotics»). Quetiapine fumarate belongs to the 3rd hazard class in terms of DL50 when administered in the stomach according to GOST 12.1.007-76 (DL50 1380-1680 mg/kg, mice and rats), has a local irritant effect: pronounced - on the mucous membrane of the eyes and moderately pronounced - on the skin. There are no signs of skin resorptive or cumulative effects of quetiapine fumarate. When inhaled, an aerosol of quetiapine fumarate has a general toxic and irritating effect in rats. The threshold of acute inhalation action of quetiapine fumarate is set at 6,2 mg/m3 for general toxic effect (effect on the quantitative composition of peripheral blood and the cardiovascular system) and irritating effect on the mucous membranes of the upper respiratory tract. For quetiapine fumarate, the tentative safe exposure level in the air of the working area is recommended at 0,2 mg/m3 , aerosol, with «+» - special protection of the skin and eyes is required. The tentative safe exposure level in the atmospheric air of urban and rural settlements is 0,002 mg/m3.
The objective of the study: evaluation of mutagenic properties of thiosonide in tests of chromosomal aberrations in mammalian bone marrow cells and mutation accounting on Salmonella typhimurium strains.Subjects and methods. Studies were carried out using F1 hybrids of CBA×C57BL/6 mice, they received thiozonide in the equivalent of a therapeutic dose and 160 times above it, once and in the course of 5 injections. The genetic toxicity of thiosonide was evaluated on Salmonella typhimurium strains in the tested doses of 1,000, 100, 10, 1 and 0.1 μg per plate.Results. No mutagenic activity of thiosonide in the chromosomal aberration counting test in bone marrow cells of mice was demonstrated. The level of chromosome aberrations in the experiment did not exceed the corresponding control values. Thus, thiosonide at the therapeutic dose (25 mg/kg) and 160-fold increase above it (4,000 mg/kg) did not induce chromosomal aberrations in the bone marrow cells of mice either with single dosing or several intragastric administrations.According to the Ames test results, the number of revertant colonies in the solvent control in the CM- and CM+ variants was within the range of spontaneous fluctuations for these strains; thiosonide in all tested doses did not show mutagenic effect on the TA 100, TA 98, and TA 97 strains both with the system metabolic activation and without it.
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