PHARMACOKINETIC PROPERTIES OF A NEW KAPPA-OPIOID ANALGESIC RU-1205 COMPOUND AT A SINGLE PERORAL ADMINISTRATION

The aim of the study is the investigation of the pharmacokinetic properties of the RU-1205 compound, with previously identified kappa-agonistic and analgesic effects, at a single oral administration, as well as comparison of the relationship between its pharmacokinetic and analgesic properties.Mater...

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Main Authors: A. A. Spasov, L. A. Smirnova, O. Yu. Grechko, N. V. Eliseeva, Yu. V. Lifanova, A. I. Rashchenko, O. N. Zhukovskaya, A. S. Morkovnik, V. A. Anisimova
Format: Article
Language:Russian
Published: Pyatigorsk Medical and Pharmaceutical Institute - branch of Volgograd State Medical University 2021-07-01
Series:Farmaciâ i Farmakologiâ (Pâtigorsk)
Subjects:
Online Access:https://www.pharmpharm.ru/jour/article/view/833
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spelling doaj-4c0fb6efffa84b93b12c9aa1990345312021-07-29T08:07:38ZrusPyatigorsk Medical and Pharmaceutical Institute - branch of Volgograd State Medical University Farmaciâ i Farmakologiâ (Pâtigorsk)2307-92662413-22412021-07-019214916010.19163/2307-9266-2021-9-2-149-160385PHARMACOKINETIC PROPERTIES OF A NEW KAPPA-OPIOID ANALGESIC RU-1205 COMPOUND AT A SINGLE PERORAL ADMINISTRATIONA. A. Spasov0L. A. Smirnova1O. Yu. Grechko2N. V. Eliseeva3Yu. V. Lifanova4A. I. Rashchenko5O. N. Zhukovskaya6A. S. Morkovnik7V. A. Anisimova8Volgograd State Medical University 1, Pavshikh Bortsov Square, Volgograd, Russia 4001311. Volgograd State Medical University 1, Pavshikh Bortsov Square, Volgograd, Russia 400131 2. Volgograd Medical Research Center; 1, Pavshikh Bortsov Square, Volgograd, Russia, 400131Volgograd State Medical University 1, Pavshikh Bortsov Square, Volgograd, Russia 400131Volgograd State Medical University 1, Pavshikh Bortsov Square, Volgograd, Russia 400131Volgograd State Medical University 1, Pavshikh Bortsov Square, Volgograd, Russia 400131Volgograd State Medical University 1, Pavshikh Bortsov Square, Volgograd, Russia 400131Scientific Research Institute of Physical and Organic Chemistry, Southern Federal University Bldg. 2, 194, Stachki Ave., Rostov-on-Don, Russia, 344090Scientific Research Institute of Physical and Organic Chemistry, Southern Federal University Bldg. 2, 194, Stachki Ave., Rostov-on-Don, Russia, 344090Scientific Research Institute of Physical and Organic Chemistry, Southern Federal University Bldg. 2, 194, Stachki Ave., Rostov-on-Don, Russia, 344090The aim of the study is the investigation of the pharmacokinetic properties of the RU-1205 compound, with previously identified kappa-agonistic and analgesic effects, at a single oral administration, as well as comparison of the relationship between its pharmacokinetic and analgesic properties.Materials and methods. Pharmacokinetic parameters of RU-1205 after the oral administration at the dose of 50 mg / kg were investigated using the method of High Performance Liquid Chromatography  with determination of the concentration of the compound according to the previously constructed calibration schedule. The indices of the area under the pharmacokinetic curve, clearance, half-life, residence time of the drug molecule in the body, a total (apparent) volume of distribution, as well as the indicator of absolute bioavailability, were calculated. The tissue distribution and excretion of RU-1205 were studied.Potential metabolites of RU-1205 were predicted using the PALLAS 3.00 program. The study of the analgesic activity was carried out on a model of central somatogenic pain with electricalstimulation, with the dynamics assessment of the voltage amplitude of the corresponding reaction of the "tail-flick" reflex.Results. The compound under study is rapidly adsorbed from the gastrointestinal tract, reaching a maximum concentration by the end of the first hour of the study, and is determined in plasma within 12 hours. Its half-life is 17.7 hours. The absolute oral bioavailability is 37.3%. It was found out that the compound is withdrawn within 3-4 days. The main route of excretion is extrarenal. Biotransformation of a substance probably proceeds mainly with the formation of oxidized forms of the initial molecule by reactions of the first phase of metabolic transformation. The analgesic effect is long-lasting: it starts after 15 minutes and lasts for 12 hours with flattening of the curve by the 8th hour.Conclusion. When administered orally, the test substance undergoes a long process of elimination, has the greatest tropism for the elimination organs and undergoes active biotransformation processes in the body of animals. As a result of it, active metabolic products with an analgesic activity are, possibly, formed.https://www.pharmpharm.ru/jour/article/view/833kappa agonistsopioid analgesicsbenzimidazolespharmacokineticsperoral routebioavailabilityexcretiontissue distribution
collection DOAJ
language Russian
format Article
sources DOAJ
author A. A. Spasov
L. A. Smirnova
O. Yu. Grechko
N. V. Eliseeva
Yu. V. Lifanova
A. I. Rashchenko
O. N. Zhukovskaya
A. S. Morkovnik
V. A. Anisimova
spellingShingle A. A. Spasov
L. A. Smirnova
O. Yu. Grechko
N. V. Eliseeva
Yu. V. Lifanova
A. I. Rashchenko
O. N. Zhukovskaya
A. S. Morkovnik
V. A. Anisimova
PHARMACOKINETIC PROPERTIES OF A NEW KAPPA-OPIOID ANALGESIC RU-1205 COMPOUND AT A SINGLE PERORAL ADMINISTRATION
Farmaciâ i Farmakologiâ (Pâtigorsk)
kappa agonists
opioid analgesics
benzimidazoles
pharmacokinetics
peroral route
bioavailability
excretion
tissue distribution
author_facet A. A. Spasov
L. A. Smirnova
O. Yu. Grechko
N. V. Eliseeva
Yu. V. Lifanova
A. I. Rashchenko
O. N. Zhukovskaya
A. S. Morkovnik
V. A. Anisimova
author_sort A. A. Spasov
title PHARMACOKINETIC PROPERTIES OF A NEW KAPPA-OPIOID ANALGESIC RU-1205 COMPOUND AT A SINGLE PERORAL ADMINISTRATION
title_short PHARMACOKINETIC PROPERTIES OF A NEW KAPPA-OPIOID ANALGESIC RU-1205 COMPOUND AT A SINGLE PERORAL ADMINISTRATION
title_full PHARMACOKINETIC PROPERTIES OF A NEW KAPPA-OPIOID ANALGESIC RU-1205 COMPOUND AT A SINGLE PERORAL ADMINISTRATION
title_fullStr PHARMACOKINETIC PROPERTIES OF A NEW KAPPA-OPIOID ANALGESIC RU-1205 COMPOUND AT A SINGLE PERORAL ADMINISTRATION
title_full_unstemmed PHARMACOKINETIC PROPERTIES OF A NEW KAPPA-OPIOID ANALGESIC RU-1205 COMPOUND AT A SINGLE PERORAL ADMINISTRATION
title_sort pharmacokinetic properties of a new kappa-opioid analgesic ru-1205 compound at a single peroral administration
publisher Pyatigorsk Medical and Pharmaceutical Institute - branch of Volgograd State Medical University
series Farmaciâ i Farmakologiâ (Pâtigorsk)
issn 2307-9266
2413-2241
publishDate 2021-07-01
description The aim of the study is the investigation of the pharmacokinetic properties of the RU-1205 compound, with previously identified kappa-agonistic and analgesic effects, at a single oral administration, as well as comparison of the relationship between its pharmacokinetic and analgesic properties.Materials and methods. Pharmacokinetic parameters of RU-1205 after the oral administration at the dose of 50 mg / kg were investigated using the method of High Performance Liquid Chromatography  with determination of the concentration of the compound according to the previously constructed calibration schedule. The indices of the area under the pharmacokinetic curve, clearance, half-life, residence time of the drug molecule in the body, a total (apparent) volume of distribution, as well as the indicator of absolute bioavailability, were calculated. The tissue distribution and excretion of RU-1205 were studied.Potential metabolites of RU-1205 were predicted using the PALLAS 3.00 program. The study of the analgesic activity was carried out on a model of central somatogenic pain with electricalstimulation, with the dynamics assessment of the voltage amplitude of the corresponding reaction of the "tail-flick" reflex.Results. The compound under study is rapidly adsorbed from the gastrointestinal tract, reaching a maximum concentration by the end of the first hour of the study, and is determined in plasma within 12 hours. Its half-life is 17.7 hours. The absolute oral bioavailability is 37.3%. It was found out that the compound is withdrawn within 3-4 days. The main route of excretion is extrarenal. Biotransformation of a substance probably proceeds mainly with the formation of oxidized forms of the initial molecule by reactions of the first phase of metabolic transformation. The analgesic effect is long-lasting: it starts after 15 minutes and lasts for 12 hours with flattening of the curve by the 8th hour.Conclusion. When administered orally, the test substance undergoes a long process of elimination, has the greatest tropism for the elimination organs and undergoes active biotransformation processes in the body of animals. As a result of it, active metabolic products with an analgesic activity are, possibly, formed.
topic kappa agonists
opioid analgesics
benzimidazoles
pharmacokinetics
peroral route
bioavailability
excretion
tissue distribution
url https://www.pharmpharm.ru/jour/article/view/833
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