Study of Acute Toxicity and Irritant Effect of Nasal Spray Naltrexone Hydrochloride

Introduction. Acute toxicity of naltrexone hydrochloride nasal spray during intragastric administration to mice and local irritant effect on rabbits was studied. At all stages of the experiment, observations were made on the General condition of the animals. The state of homeostasis was evaluated using functional, hematological and morphometric methods. According to the results of research, there was no local irritant effect on the eyes of rabbits, as well as no toxic effect of high doses of the drug on animals. Introduction. Naltrexone hydrochloride in doses of 1.5– 5 mg/day has shown its effectiveness in the treatment of a number of diseases. Due to the lack of such a "low-dose" naltrexone registered on the pharmaceutical market, we have developed the composition of the nasal spray naltrexone hydrochloride. One of the stages of our research is to study the safety of the drug being developed. The first step in this direction was to study its acute toxicity and local irritant effect.
Aim. Study of acute toxicity and local irritant effect of naltrexone hydrochloride nasal spray.
Materials and methods. The object of the study was a nasal spray of naltrexone hydrochloride. Acute toxicity studies were performed on outbred adult mice (females). Study of local irritant effect on Soviet chinchilla rabbits (males).
Results and discussion. The study of acute toxicity showed that the drug, at a dose significantly higher than the estimated maximum daily therapeutic dose for humans, did not have a significant toxic effect on the body of laboratory animals. The presence of a local irritant effect in the studied drug was not established in the framework of the experiment.
Conclusion. As part of the experiment, the drug under study did not have a local irritant or toxic effect on the animal body. The results obtained allow us to continue the development and study of the nasal spray naltrexone hydrochloride.

1. Toljan K., Vrooman B. Low-Dose Naltrexone (LDN) – review of therapeutic utilization. Medical Sciences. 2018;6(4):82. DOI: 10.3390/medsci6040082.

2. Domnina Y. M., Kedik S. A., Suslov V. V., Shnyak E. A. Rationale for the selection of auxiliary components for the naltrexone hydrochloride nasal spray. Razrabotka i registratsiya lekarstvennykh sredstv = Drug development & registration. 2018;(4):73–77. (In Russ.)

3. GOST R 56701-2015 "Lekarstvennye sredstva dlya meditsinskogo primeneniya. Rukovodstvo po planirovaniyu doklinicheskikh issledovaniy bezopasnosti s tsel'yu posleduyushchego provedeniya klinicheskikh issledovaniy i registratsii lekarstvennykh sredstv" [Medicinal products for medical use. Guidelines for planning preclinical safety studies for subsequent clinical trials and drug registration]. Available at: http://docs.cntd.ru/document/1200126923. (In Russ.)

4. Sanitary and epidemiological rules SP 2.2.1.3218-14 “Sanitarnoepidemiologicheskie trebovaniya k ustrojstvu, oborudovaniyu i soderzhaniyu eksperimental'no-biologicheskih klinik (vivariev)" [Sanitary and epidemiological requirements for the device, equipment and maintenance of experimental biological clinics (vivariums)] (approved Decree of the Chief State Sanitary Doctor of the Russian Federation of August 29, 2014, No. 51). Available at: http://docs.cntd.ru/document/420219460. (In Russ.)

5. European Convention for the Protection of Vertebrate Animals Used for Experimental and other Scientific Purposes (ETS 123). Strasbourg, 1986.

6. Mironov A. N., editor. Rukovodstvo po provedeniyu doklinicheskih issledovaniy lekarstvennyh sredstv [Guide to preclinical research of medicines]. Part 1. Moscow: Grif i K; 2013. 944 p. (In Russ.)