THE RESULTS OF THE CHRONIC TOXICITY STUDIES OF “DOLOSAN FORTE®” TABLETS
DOI:
https://doi.org/10.11603/2312-0967.2017.1.7531Keywords:
chronic toxicity, zirilon (2, 4-dichlorobenzoic acid potassium salt), pitofenone hydrochloride, fenpiverinium bromide, combination, rats, rabbits.Abstract
The aim of the study. Evaluation the level of safety of a new combined spasmoanalgetic tablets “Dolosan Forte®” – after chronic administration.
Materials and Methods. The tablets “Dolosan Forte®” were worked out by PJSC "Red Star," their composition includes zirilon (2.4-dichlorobenzoic acid potassium salt possessing a signi cant analgesic and anti-in ammatory action), pitofenone hydrochloride (myotropic spasmolytic), and fenpiverinium bromide (M-cholinolytic with additional myotropic and analgesic properties). The chronic toxicity of this drug was studied using the standard protocol presupposing the 30–day course of administration to rats at doses of 2.3 and 23 mg/kg; and rabbits at doses of 1 and 10 mg/kg.
Results and Discussion. There was no evidence of intoxication, disturbances of the processes of growth and development, as well as hematological parameters, biochemical parameters of blood and urine, functional state of central nervous system (in the "open eld" test), the kidneys (under the conditions of water diuresis), and myocardium (according to electrocardiogram). According to data obtained in the histological studies, no signs of cardiotoxic, hepatotoxic, and nephrotoxic action of the drug, neither symptoms of the irritating effect on the mucous membranes of the gastrointestinal tract were registered. Also, there was no evidence of the disturbance of the morphofunctional state of the lungs, spleen, thymus, adrenal glands, thyroid gland.
Conclusions. The study con rmed the absence of toxic effects of “Dolosan Forte®” after 30-day course of intragastric administration to rats and rabbits at a conventional therapeutic dose and at a conventional increased tenfold therapeutic dose.References
Turk DC, Wilson HD, Cahana A. Treatment of chronic non-cancer pain. Lancet. 2011;377:2226. DOI: 10.1016/ S0140-6736(11)60402-9
Hedenmalm K, Spigset O. Agranulocytosis and other blood dyscrasias associated with dipyrone (metamizole). Eur J Clin Pharmacol. 2002;58(4):265–4. DOI: 10.1007/ s00228-002-0465-2
Yakovleva LV, Shapoval OM, Levitin IeIa. [Comparative characteristics of the pharmacological action of a series of benzoic acid derivatives]. Visnyk farmatsii. 2001;3(27):172–3. Ukrainian.
Trutaev SI, Shtrygol SYu, Kovalova IO, Shtrygol YuYu. [An experimental study of “Dolosan Forte®” tablets analgesic, antiinammatory and antispasmodic activity]. Farmacom (Kharkiv). 2016;2:50–4. Ukrainian.
Golhar KB, Gupta RL. Open labelled evaluation of in-jection Manyana (a combination of diclofenac + pitofenone + fenpiverinium) in ureteric, biliary and intestinal spasm–apreliminary report. J Indian Med Assoc. 1999;97(9):398– 400.
Preclinical studies of drugs. Ed. O.V. Stefanov. Kyiv: Avicenna; 2001: 90–7. Ukrainian.
Drug discovery. Good laboratory practice. [Належна лабораторна практика] Kyiv: Ministry of Health of Ukraine; 2001. Ukrainian.
Animal use in toxicity studies. In: The ethics of research involving animals. – London: Nuf eld Council on Bioethics, 2005:153–68.
Kamyshnikov VS. Handbook of clinical and biochemical laboratory diagnostics. [Справочник по клинико-биохимической лабораторной диагностике]. Minsk: Belarus; 2000. Russian.
Laboratory tests in the clinic. Ed. V.V. Menshikov. Moscow: Medicine; 1987. Russian.
Altgauzen AJa. Clinical laboratory studies. [Лабораторные клинические исследования] Moscow:Medicine; 1987:158. Russian.
Merkulov GA. Course of histological techniques. [Курс патологистологической техники] Moscow: Medicine; 1969. Russian.
Zapadniuk IP, Zapadniuk VI, Zahariia EA, Zapadniuk BV. Laboratory animals. Breeding, maintenance, use in the experiment. [Лабораторные животные. Разведение, содержание, использование в эксперименте] Kyiv: High School; 1983:249. Russian.
Side effects of drugs. Eds. Drogovoz SM, Gudzenko AP, Butko YaA. Kharkiv:«SIM»; 2010. Russian.
Peresada O. A. The concept of dysmenorrhea and modern therapeutic approaches: experience of Spazmalgon. Reproduktivnoe zdorove Vostochnaya Evropa. 2016;3(45):403–10. Russian.
Syrovaya AO. Experimental and quantum – chemical ground of combined antiinammatory drug creation. Extended abstract of doctor’s thesis. Kharkiv; 2011. Ukrainian.
Tabeeva GR. Intricate simple analgesics, or what is necessary to keep in mind when choosing an analgesic. Russkiy meditsinskiy zhurnal. 2013;21(10):470–5. Russian.
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