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Prodrugs for Improved Oral β-Estradiol Bioavailability

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Abstract

Prodrugs of β-estradiol (1) were prepared with the objective of improving its oral bioavailability. β-Estradiol-3-acetylsalicylate (2), β-estradiol-3-salicylate (3), and β-estradiol-3-anthranilate (4) were synthesized. With these prodrugs the 3-phenolic hydroxy group of estradiol was protected, so that first-pass conjugative metabolism could be reduced. Prodrug hydrolysis rates in dog and human plasma in vitro were determined. Deacetylation of estradiol-3-acetylsalicylate was much more rapid than its hydrolysis to estradiol. In dogs, oral estradiol bioavailability after administration of 2 and 4 was 17-fold and 5-fold higher, respectively, than after oral 1.

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Hussain, M.A., Aungst, B.J. & Shefter, E. Prodrugs for Improved Oral β-Estradiol Bioavailability. Pharm Res 5, 44–47 (1988). https://doi.org/10.1023/A:1015863412137

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  • DOI: https://doi.org/10.1023/A:1015863412137

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