danДоклады Национальной академии наук БеларусиDoklady of the National Academy of Sciences of Belarus1561-83232524-2431The Republican Unitary Enterprise Publishing House "Belaruskaya Navuka"dan-15Research ArticleХИМИЯCHEMISTRYФАРМАКОКИНЕТИЧЕСКИЕ СВОЙСТВА И ЭНЗИМАТИЧЕСКИЙ ГИДРОЛИЗ ДИАЦИЛГЛИЦЕРОФОСФАТНЫХ ПРОИЗВОДНЫХ ФЛУДАРАБИНАPHARMACOKINETIC PROPERTIES AND THE ENZYMATIC HYDROLYSIS OF DIACYLGLYCEROPHOSPHATE FLUDARABINE DERIVATIVESЦИБУЛЬСКАЯИ. А.TSYBULSKAYAI. A.ilonaolenikova@tut.byКУЛАКТ. И.KULAKT. I.kulak@iboch.bas-net.byБУРАВСКАЯТ. Н.BURAVSKAYAT. N.buravskaya@iboch.bas-net.byГОЛУБЕВАМ. Б.GOLUBEVAM. B.ШАБУНЯП. С.SHABUNYAP. S.ФАТЫХОВАС. А.FATYKHOVAS. A.iboh_lfhi@rambler.ruКУРМАНП. В.KURMANP. V.peter_kurman@tut.byКАЛИНИЧЕНКОЕ. Н.KALINICHENKOE. N.

член-корреспондент

kalinichenko@iboch.bas-net.byИнститут биоорганической химии НАН Беларуси, МинскInstitute of Bioorganic Chemistry, Minsk2016210520166016571Copyright © ЦИБУЛЬСКАЯ И.А., КУЛАК Т.И., БУРАВСКАЯ Т.Н., ГОЛУБЕВА М.Б., ШАБУНЯ П.С., ФАТЫХОВА С.А., КУРМАН П.В., КАЛИНИЧЕНКО Е.Н., 20162016ЦИБУЛЬСКАЯ И.А., КУЛАК Т.И., БУРАВСКАЯ Т.Н., ГОЛУБЕВА М.Б., ШАБУНЯ П.С., ФАТЫХОВА С.А., КУРМАН П.В., КАЛИНИЧЕНКО Е.Н.TSYBULSKAYA I.A., KULAK T.I., BURAVSKAYA T.N., GOLUBEVA M.B., SHABUNYA P.S., FATYKHOVA S.A., KURMAN P.V., KALINICHENKO E.N.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://doklady.belnauka.by/jour/article/view/15

Установлено, что в результате внутрижелудочного введения 1,2- и 1,3-диацилглицерофосфатных производных флударабина крысам Вистар и аутбредным мышам наблюдается пролонгированное выделение и более длительная циркуляция нуклеозида в системном кровотоке животных, чем после введения эквимолярных количеств флударабина фосфата. Изученные фосфолипидные производные могут рассматриваться в качестве пероральных пролекарств флударабина. Показано, что оральная биодоступность флударабина из его 1,2-димиристоилглицерофосфатного производного у животных близка к его оральной биодоступности из эквимолярного количества флударабина фосфата. На основании данных, полученных в модельных экспериментах in vitro, можно предположить, что флударабин может выделяться из полученных пролекарств под действием ферментов, принадлежащих к семействам фосфолипаз А и Д, а также фосфодиэстераз.

It is shown that the intragastric administration of 1,2- and 1,3-diacylglycerphosphate fludarabine derivatives to Wistar rats and ICR outbred mice leads to a prolonged circulation of fludarabine in animal serum in comparison with the analogous administration of equimolar fludarabine phosphate. The investigated compounds can be regarded as oral fludarabine prodrugs. It is found that the oral bioavalability of fludarabine from its 1,2-dimyristoylglycerophosphate derivative is close to its oral bioavalability from equimolar fludarabine phosphate. Based on the data of the model in vitro experiments, we can suppose that fludarabine can release from its diacylglycerphosphate prodrugs under the action of phospholipases A and D and phosphodiesterases.

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The authors declare that there are no conflicts of interest present.