Distribution, excretion and metabolic pathways of a single parenteral administration of kappa-opioid receptor agonist RU-1205

Author:

Spasov Alexander A.,Smirnova Lyudmila A.,Grechko Olesya Iu.,Eliseeva Natalya V.,Lifanova Yuliya V.ORCID,Rashchenko Andrey I.,Zhukowskaia Olga N.,Morkovnik Anatoly S.,Anisimova Vera A.,Syrvacheva Olga E.

Abstract

Introduction: The purpose was to study the pharmacokinetic properties of RU-1205 with the previously identified kappa-agonistic and analgesic effects after parenteral administration. Materials and methods: Pharmacokinetic parameters of RU-1205 after intravenous and subcutaneous administration at doses of 10 mg/kg and 50 mg/kg, respectively, were investigated, using the method of high-performance liquid chromatography with measurement of the compound according to a pre-established calibration curve. The indices of the area under the pharmacokinetic curve, clearance, half-life, residence time of the drug molecule in the body, total (apparent) volume of distribution, as well as the indicator of absolute bioavailability for subcutaneous administration were calculated. Tissue distribution and excretion of RU-1205 were also studied. Evaluation of metabolism of RU-1205 was conducted in silico, using the PALLAS 3.00 software, with the use of specific tests with CYP 450 substrates and by studying the ability of RU-1205 to form conjugates with endogenous acids. Results and discussion: It was found that after a single intravenous administration, the investigated substance was determined in the blood for 12 h; the half-life was 8.49 hours. The absolute bioavailability after subcutaneous administration is 57.35%. RU-1205 is eliminated within 3–4 days. The main route of excretion is extrarenal. The biotransformation of the substance probably proceeds mainly with the formation of oxidized forms of the initial molecule according to the reactions of the first phase of metabolic transformation, so the chance to observe phase 2 of the metabolism could be very low. Conclusion: The test substance undergoes a long process of elimination, has the highest tropism to the elimination organs and undergoes active biotransformation processes in the body of animals.

Publisher

Pensoft Publishers

Subject

Pharmacology (medical),Pharmacology

Cited by 1 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

1. Effects of a New Kappa Agonist (Fluorophenyl Derivative of Imidazo[1,2-<i>а</i>]benzimidazole) on the Rat Genome;Bulletin of the Scientific Centre for Expert Evaluation of Medicinal Products. Regulatory Research and Medicine Evaluation;2023-01-18

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