PHARMACOKINETIC PROPERTIES AND THE ENZYMATIC HYDROLYSIS OF DIACYLGLYCEROPHOSPHATE FLUDARABINE DERIVATIVES
Abstract
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.
About the Authors
I. A. TSYBULSKAYA
Institute of Bioorganic Chemistry, Minsk
Belarus
Belarus
T. I. KULAK
Institute of Bioorganic Chemistry, Minsk
Belarus
Belarus
T. N. BURAVSKAYA
Institute of Bioorganic Chemistry, Minsk
Belarus
Belarus
M. B. GOLUBEVA
Institute of Bioorganic Chemistry, Minsk
Belarus
Belarus
P. S. SHABUNYA
Institute of Bioorganic Chemistry, Minsk
Belarus
Belarus
S. A. FATYKHOVA
Institute of Bioorganic Chemistry, Minsk
Belarus
Belarus
P. V. KURMAN
Institute of Bioorganic Chemistry, Minsk
Belarus
Belarus
E. N. KALINICHENKO
Institute of Bioorganic Chemistry, Minsk
Belarus
Belarus
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