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Vol. 23, Art. 43 (pp. 722-732)    |    2022       

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Evaluation of the pharmacokinetics of perfluorodecalin in whole blood and lungs of rats with single endotracheal and intragastric introduction

Barinov V.A.1, Ostrovidova E.V.1, Belyakova N.A.1, Bonitenko E.U.1,2, Trefilov V.V.1, Utsal V.A.1, Lugovkina N.V.1, Barinov V.V.1

1 FGBI «Scientific and Clinical Center of Toxicology named after S.N. Golikov of the Federal Medical and Biological Agency»

2 FGAOU GU «Sevastopol State University»

Brief summary

The relevance of studying the safety, toxicokinetics and pharmacokinetics of perfluoroorganic compounds is determined by the development in medicine of a promising direction for their use as agents for therapeutic bronchoalveolar lavage, systems for transporting drugs to the lungs, as well as gas transport respiratory fluids for the developed technologies of liquid ventilation of the lungs, including options for partial, full and gas-liquid ventilation. An important role in this is played by the evaluation of pharmacokinetic parameters, which allow one to get an idea of the patterns of intake, distribution and excretion of perfluoroorganic compounds from the body during the endotracheal route of their administration. Aim. Study of the pharmacokinetics of perfluorodecalin in whole blood and in the lungs of mature albino rats with a single intragastric and endotracheal routes of administration. Materials and methods. Perfluorodecalin (CAS 306-94-5) was used in the experiment. The experiments were carried out on mature white male Wistar rats. To determined perfluorodecalin in whole blood and lung tissues, gas-liquid chromatography-mass spectrometry is used. A preparation required liquid extraction of the target compound from the biomaterial with heptane, using perfluorobenzene as an internal standard. Results. As a result of the study of the content of perfluorodecalin in samples of whole blood and lungs of rats using the method of gas-liquid chromatography-mass spectrometry, it was shown that this substance is characterized by a non-standard distribution process upon endotracheal administration. In this regard, the analysis of pharmacokinetic curves is possible using a model-independent method. Perfluorodecalin is characterized by very low bioavailability in both endotracheal and intragastric routes of its introduction into the body. No metabolites of perfluorodecalin were found in biosamples, which confirms its high chemical stability. Conclusions. Since perfluorodecalin is not metabolized in the body and has a tropism for fat-rich tissues, it belongs to slowly excreted substances, and three stages can be distinguished in its distribution and elimination from the body. The first stage is associated with the presence of non-absorbed perfluorodecalin in the lungs or in the gastrointestinal tract. The second stage takes place against the background of a significant reduction or even cessation of perfluorodecalin intake from the injection site and complex processes of its redistribution between organs and tissues, mainly rich in fats. The third stage is associated with prolonged excretion of perfluorodecalin from the body, mainly through the lungs.


Key words

perfluorodecalin, liquid lung ventilation, bronchoalveolar lavage, preclinical pharmacokinetic study, white rats, endotracheal administration, intragastric administration, whole blood, lungs, gas-liquid chromatography-mass spectrometry

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