Pharmacokinetics of a New Dimethylamineethanol Derivative Administered Orally to Laboratory Animals

Abstract

A new derivative of dimethylaminoethanol, butanedioic and trans-butenedioic acids (laboratory code ADK-17) was synthesized at the Organic Chemistry Department of the Saint Petersburg State Chemical and Pharmaceutical University (SPSPU). This promising nootropic and anti-asthmatic agent is planned for use in an oral dosage form. The aim was to calculate the pharmacokinetic parameters of the synthesized compound and to determine its possible biotransformation pathways. Rabbits of the Soviet Chinchilla breed were used as a test system in the preclinical study of the compound pharmacokinetics. In accordance with the designed schedule, blood was taken from the marginal vein of the ear, and urine samples were taken. Quantitative determination in biological media was carried out using an Ultimate 3000 liquid chromatograph with a Q-Exactive mass-selective detector with electrospray ionization in accordance with OFS 1.2.1.100015 (Chromatography) of the State Pharmacopoeia by ultra-performance liquid chromatography–mass spectrometry (UPLC-MS). To study the pharmacokinetics of the ADK-17 preparation, a measurement procedure was developed with a detection limit in biological media ranging from 10-6 to 10-3 mg/ml. The determined harmacokinetic parameters show that the absorption of ADK-17 into the systemic circulation from the gastrointestinal tract occurs at an average rate, with its maximum concentration in blood plasma during the oral route of administration being observed between 60–90 min. The elimination half-life from the systemic circulation comprises 4.3 h. Urinary excretion in the first 4 h proceeds at a high rate; however, the compound is detected in the urine within 3 days and in the blood within 2 days from the moment of administration.