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THE STUDY OF THE PHARMACOKINETIC PROPERTIES OF 11-DEOXYMISOPROSTOL AFTER INTRAGASTRIC ADMINISTRATION

https://doi.org/10.47093/22187332.2019.1.22-28

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Abstract

The aim - to establish the main pharmacokinetic parameters of 11-deoxyimisoprostol after intragastric administration. Materials and methods. The experiments were performed on 410 white outbred rats - females weighing 180-220 g. 11-deoxymysoprostol was administered to rats intragastrally at a dose of 2.0 mg/kg. Blood and organs were taken for examination at 6, 12, 15, 30 minutes and hourly for 12 hours after administration. After these intervals, the concentration of the drug in the blood and tissue homogenates of laboratory animals was determined, and in the urine - every hour during the day. Chromatographic separation was carried out using a liquid chromatograph (Shimadzu, Japan LC-20 PROMI- NENCE with a diode - array detector SPD-20A).Results. 11-deoxyimisoprostol is rapidly absorbed from the gastrointestinal tract. The maximum (6.625 μg/ml) of the compound in the blood plasma is reached 15 minutes after intragastric administration. When this occurs, a simultaneous in - crease in the concentration of the metabolite - 11-deoxyimisoprostolic acid. The maximum concentration (23.547 µg/ml) of the metabolite in the blood plasma is reached 30 minutes after the administration of 11-deoxyimisoprostol. 11-deoxyimisoprostol is intensively distributed throughout the organs and tissues, while the compound has the highest affinity for myometrium and liver. The smallest quantities of the test substance were found in the lungs, the brain, and the omentum. The active metabolite of 11-deoxyimisoprostol is intensively distributed in organs and tissues, while in the greatest amounts it was detected in the myometrium and the liver and kidneys. The smallest quantities of the test substance were found in the lungs, the brain, and the omentum. In the urine, 11-deoxyimisoprostolic acid is determined during the first days of the study, with a maximum clearance of 6-8 hours after administration.Conclusion. 11-deoxyimisoprostol has a short half - life after intragastric administration (T1/2=0,550 h), which indicates the absence of cumulative properties. The nature of the pharmacokinetic curve is monoexponential.

About the Authors

R. M. Kataeva
Bashkir State Medical University
Russian Federation


E. F. Agletdinov
Vector-Best
Russian Federation


K. V. Bulygin
I.M. Sechenov First Moscow State Medical University (Sechenov University); M.V. Lomonosov Moscow State University
Russian Federation


V. A. Kataev
Bashkir State Medical University
Russian Federation


N. A. Ivanova
Ufa Institute of Chemistry of the Ufa Federal Research Center of the Russian Academy of Sciences
Russian Federation


S. F. Gabdrakhmanova
Ufa Institute of Chemistry of the Ufa Federal Research Center of the Russian Academy of Sciences
Russian Federation


T. A. Sapozhnikova
Ufa Institute of Chemistry of the Ufa Federal Research Center of the Russian Academy of Sciences
Russian Federation


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ISSN 2218-7332 (Print)
ISSN 2658-3348 (Online)