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The list of sanitary standards with the mark "absent" should include antitumor cytostatics as the drugs satisfying the following criteria: extreme hazard and toxicity, late adverse effects, primarily mutagenic and carcinogenic properties; lack of highly sensitive methods for their determination in water; lack of 100%-efficiency methods for sewage purification. A complex of protective measures is justified and sanitary recommendations are given to protect the aqueous environment during cytostatic production.

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Results of experimental substantiation of hygienic standards of 30 drugs in water and analysis of published data showed that drugs should be referred to highly hazardous pollutants of the environment. Criteria and indexes of pharmacologic activity were proposed for use in norm-setting studies.

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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.

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The antihistaminic drug dimebon was subjected to toxicological study. It was demonstrated that as regards the level of the mean lethal doses dimebon can be attributed to little toxic substances. Administration of the drug in the doses approximating the therapeutic ones (1 and 5 mg/kg) for 2 months did not produce any alterations in rats, guinea-pigs or dogs. When administered in high doses (10 and 70 mg/kg) the drug provoked compensated abnormalities of some functions of the liver and kidneys in the presence of moderate and reversible structural changes in these organs. Dimebon did not exert any local irritating effect on the gastrointestinal tract. Administration of the drug in doses of 150 and 300 mg/kg at different times of pregnancy (days 1-7, 8-13, 14-19) did not produce any embryolethal or teratogenic effects.

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A study was made of the blastomogenic activity of dioxydin, a new antibacterial broad-action drug. Administration of dioxydin in doses of 20-100 mg/kg (exceeding 2-10-fold the therapeutic dose for humans) to mice and rats intragastrically for 18 months and intraperitoneally (2 years of observation) as well as combined administration of the drug to rats transplacentally and postnatally (1.5 years of observation) did not induce any neoplasms.

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The first generation progeny of rats received days 10-13 of pregnancy a new antiviral drug bonaphthon (400 mg/kg) which exerts a toxic effect on females. The progeny did not show postnatal death or reduction of the life span. Moreover, no impairment of muscle work capacity, basal metabolism, cardiovascular system, peripheral blood parameters, or changes in the function of organs and systems were recorded. Morphological and functional deviations in the liver of 2-month-old progeny were unstable and got repaired by 3 months of age.

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The toxicity of the original drug bonaphthon was studied in pregnant and nonpregnant mice and rats given the drug orally and intraperitoneally. In a dose of 100 mg/kg bonaphthon had no toxic effect on pregnant rats after 4-time administration per os, while in a single dose of 400 mg/kg the drug elicited side effects such as congestion phenomena and inconsistent dystrophic changes in the parenchymal organs. Toxic effects in the liver were most pronounced when the drug was administered in the earlier periods of pregnancy.

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The ability of 14C-bonafton to penetrate the placental bar was studied in female Wistar rats. The drug was shown to penetrate through the placenta in insignificant amounts. The maximal quantities of the drug which entered the fetuses proper during the last third of pregnancy do not exceed 0.55% of 14C-bonafton content in the mother's blood. It was revealed that bonafton transplacental penetration is barred by fetal envelopes.

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The parameters of bonafton pharmacokinetics (absorption, distribution, excretion) have been studied in male Wistar rats at single enteral and intraperitoneal administration. With these routes of administration daily resorption amounts to 26 and 100%, respectively. Regardless administration routes 14C-bonafton distributes in a similar way in the internal organs and tissues and is excreted through the kidneys and gastrointestinal tract, the latter way of excretion being predominant. T1 = 0.25 day (24%) and T2 = 1.8 day. A two-chamber model of the drug metabolism is suggested. This model allows a calculation of bonafton and its metabolites accumulation at repeated administration of the drug to the body.

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Results of testing the embryotropic activity of bonaphthone used in different doses (700; 400; 100; 50 and 2 mg/kg) are reported. With its oral introduction to pregnant rats bonaphthone, given in doses at the level of the therapeutid one (2 mg/kg) and exceeding it by as much as 25 times (50 mg/kg), was found not to produce any damaging effect on the fetus. With its action in doses of 100 and 400 mg/kg a slight embryotoxic effect was noted. In the sublethal dose of 700 mg/kg the preparation displays a moderate embryotoxic action and produces a number of circulatory changes in the fetuses. It is concluded that bonaphthone displays no teratogenic properties.

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