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Vol. 22, Art. 26 (pp. 372-388)    |    2021       

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The research of acute toxicity indicators in inhalation of antiemetics

Ivanov I.M., Alhutova I.M., Shyryava A.I., Vengerovich N.G., Raguzin E.V., Nikiforov A.S., Vetryakov O.V.

1 FSBI "State Research and Testing Institute of Military Medicine" of the Ministry of Defense of the Russian Federation, Lesoparkovaya st. 4, Saint Petersburg, Russia
2Military Medical Academy named after S. M. Kirov, Lebedeva st., 6, Saint Petersburg, Russia

Brief summary

The inhalation of antiemetics is considered to be an alternative to other routes of drug administration (intravenous (IV), oral (PO)) for the improvement of patient comfort and for use in emergency situations. An important part of research aimed at creation of inhaled forms of antiemetics is the study of their tolerance in terms of external respiration and physical performance dysfunctions. In experiments on rats, toxic properties of three antiemetic drugs (ondansetron, metoclopramide and palonosetron) following intratracheal administration were characterized. The drugs were characterized by a similar level of median lethal doses, which were 20.3?1.75, 44.3?5.24 and 40.1?2.54 mg/kg for ondansetron, metoclopramide and palonosetron respectively. The acute toxicity of palonosetron, ondansetron and metoclopramide with i/t and i/v administration was comparable, which may indirectly indicate high bioavailability of these drugs when inhaled. The drugs administered at a single dose had no effect on the indicators of external respiration function (ERF) and physical performance of rats in the weight-loaded forced swimming test. In a daily dose metoclopramide was characterized by the worst tolerance indicators (it caused severe disturbances in the function of external respiration and physical performance), while palonosetron - by the best ones. The data obtained allow us to consider palonosetron as a promising drug for the development of a dosage form powder for inhalation in capsules for use in individual dry powder inhalers.


Key words

antiemetic drugs, emetic syndrome, primary reaction to radiation, palonosetron, ondansetron, metoclopramide, inhalation administration, intratracheal administration, respiratory function, physical performance

Reference list

1. Perspektivi razvitiya tehnicheskih sredstv i lekarstvennih form dlya primeneniya medicinskih sredstv zashiti / I. M. Ivanov, S. V. Chepyr, A. S. Nikiforov [i dr.] // Voenno-medicinskii jyrnal. - 2019. - T. 340. - 4. - S. 47-53.


2. Obosnovanie trebovanii k perspektivnim tehnicheskim sredstvam ingalyacionnoi dostavki lekarstvennih preparatov dlya primeneniya na etapah medicinskoi evakyacii / I. M. Ivanov, A. S. Nikiforov, S. V. Chepyr [i dr.] // Medline.ru. Rossiiskii biomedicinskii jyrnal. - 2019. - T. 20. - 1. - S. 110-133.


3. Prikaz Ministerstva zdravoohraneniya RF ? 70n ot 15 fevralya 2013 g. «Ob ytverjdenii trebovanii k komplektacii lekarstvennimi preparatami i medicinskimi izdeliyami komplekta individyalnogo medicinskogo grajdanskoi zashiti dlya okazaniya pervichnoi mediko-sanitarnoi pomoshi i pervoi pomoshi». URL: http://www.mchs.gov.ru/document/446399 (data obrasheniya 15.07.2021).


4. Instrykciya po primeneniu lekarstvennogo preparata dlya medicinskogo primeneniya latran // FGYP NPC «Farmzashita» FMBA Rossii : [sait]. URL: https://www.atompharm.ru/latrant (data obrasheniya: 19.07.2021).


5. Dennis, Jensen Inhaled Ondansetron & Dyspnea / Jensen Dennis. // ClinicalTrials.gov is a resource provided by the U.S. National Library of Medicine. : [sait]. URL: https://clinicaltrials.gov/ct2/show/NCT01851993 (data obrasheniya: 19.07.2021).


6. Formylyar lekarstvennih sredstv medicinskoi slyjbi Vooryjѐnnih Sil Rossiiskoi Federacii (pyatoe izdanie) / pod obshei redakciei d-ra med. nayk, prof A.Ya. Fisyna i d-ra farm.nayk, prof. U.V. Miroshnichenko - M.: GVKG im. Byrdenko, 2014. - 178 s.


7. Instrykciya po primeneniu lekarstvennogo preparata dlya medicinskogo primeneniya Metoklopramid (PN002081/01-270110).


8. Perspektivi razrabotki ingalyacionnih preparatov dlya okazaniya dogospitalnoi pomoshi porajennim avariino-opasnimi himicheskimi veshestvami / I. M. Ivanov, A. S. Nikiforov, M. A. Udin [i dr.] // Vestnik Rossiiskoi Voenno-medicinskoi akademii. - 2020. - 3(71). - S. 176-181.


9. Itogi i perspektivi sovershenstvovaniya sredstv i metodov medicinskoi zashiti ot neblagopriyatnih faktorov himicheskoi prirodi / E. V. Ivchenko, A. A. Kyzmin, V. P. Fedonuk [i dr.] // Voenno-medicinskii jyrnal. - 2019. - T. 340. - 9. - S. 14-21.


10. Rykovodstvo po provedeniu doklinicheskih issledovanii lekarstvennih sredstv. Chast pervaya / Pod red. A.N. Mironova. ? M.: Grif i K, 2013. 944 s.


11. Determining when enhanced pause (Penh) is sensitive to changes in specific airway resistance / G. F. David, S. R. Jeffrey, C. J. Mark. // J Toxicol Environ Health A. 2011. 74(5). P. 287-295.


12. Biomedicinskoe (doklinicheskoe) izychenie lekarstvennih sredstv, vliyaushih na fizicheskyu rabotosposobnost: metodicheskie rekomendacii / Ministerstvo zdravoohraneniya Rossiiskoi Federacii, Federalnoe mediko biologicheskoe agentstvo. Moskva, 2017. 134 s.


13. Pharmacological comparison of human homomeric 5-HT3A receptors versus heteromeric 5-HT3A/3B receptors / CA Brady, IM Stanford, I. Ali [et al.] // Neuropharmacology. 2001. 41 (2). P. 282-286.


14. Ocherki sportivnoi farmakologii / N.N. Karnishenko, V.V. Yiba, E.B. Shystov. // Vektori ekstrapolyacii T.1. Moskva, Sankt-Peterbyrg: Aising, 2013. S. 288.


15. Dawson C. Swimming in small laboratory animals / C. Dawson, Horvath S. // Med. Sci. Sports, 1970 Vol. 2. P. 51-78.


16. Prakticheskie rekomendacii po profilaktike i lecheniu toshnoti i rvoti y onkologicheskih bolnih / L. U. Vladimirova, A.O. Gladkov, I.A. Koroleva [i dr.] // Zlokachestvennie opyholi. 2020. T. 2 . S. 24-34.


17. Horasawa, S. S. Horasawa Y. Nakamura S. Shimada. 342P Comparison of 0.25 mg versus 0.75 mg of palonosetron in combination with aprepitant and dexamethasone for prevention of chemotherapy-induced nausea and vomiting following cisplatin-containing chemotherapy in patients with esophageal cancer /Annals of Oncology // Vol. 31 P. 1374.


18. PALONOSETRON HYDROCHLORIDE INJECTION - FULL PRESCRIBING INFORMATION. // : [sait]. URL: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/208109s001lbl.pdf (data obrasheniya: 15.07.2021).


19. Efficacy, safety and pharmacokinetics of palonosetron in patients receiving highly emetogenic cisplatin-based chemotherapy: a dose-ranging clinical study / E. P., FR MacKintosh, P. Ritch [et al.]. // Ann Oncol. ? 2004 Feb. 15(2). P. 330-337.


20. David, B. J. Pharmacology / Toxicology Review And Evaluation. ALOXI? (palonosetron HCl) Capsules / B. J. David. // Department of health and human services public health service food and drug administration center for drug evaluation and research. 2008: Helsinn Healthcare SA, 2008. S. Application Number: P. 22-233.


21. Biowaiver Monographs for Immediate Release Solid Oral Dosage Forms: Metoclopramide Hydrochloride / A.G. Stosik, H.E. Junginger, S. KOPP // Journal of pharmaceutical sciences. 2007. 9. P. 3701-3708.


22. Hospira METOCLOPRAMIDE (Metoclopramide Hydrochloride Injection)/ MATERIAL SAFETY DATA SHEET/ [Elektronnii resyrs]. Rejim dostypa: https://723462.app.netsuite.com/core/media/media.nlid=12063&c=723462&h=6e976e43f9e0d52cd401&_xt=.pdf]


23. Pharmacokinetics, metabolism and excretion of intravenous [l4C]-palonosetron in healthy human volunteers / R. Stoltz, S. Parisi, A. Shah, A. Macciocchi. // Biopharm Drug Dispos. 2004 Nov. 25(8). P. 329-366..


24. Pharmacological comparison of human homomeric 5-HT3A receptors versus heteromeric 5-HT3A/3B receptors / C. A. Brady, I. M. Stanford, I. Ali [et al.]. // Neuropharmacology. 2001 Aug. 41 (2). P. 282-286.