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• W3005412519 abstract "To increase the success rate in development of prodrugs, we sought to establish a systematic in vitro method to appropriately select candidate prodrugs. Physicochemical/biopharmaceutical properties of 21 commercially available prodrugs (16 with improved membrane permeability of pharmacologically active metabolites and 5 with improved solubility) and their active metabolites were characterized in terms of solubility in artificial intestinal fluids and membrane permeability using Caco-2 cells. Their in vitro metabolic profiles were also evaluated, using human and animal enterocytes, hepatocytes, and sera. Log D values of prodrugs with improved membrane permeability were higher than those of their active metabolites, whereas those of prodrugs with improved aqueous solubility were lower than those of active metabolites. The prodrugs with improved aqueous solubility were highly soluble in artificial intestinal fluids. All prodrugs were efficiently converted to active metabolites with human matrices, whereas some were not with dog or monkey matrices. This study demonstrated that physicochemical/biopharmaceutical properties could be useful information to facilitate design of prodrugs and for selection of candidate prodrugs. Moreover, the in vitro evaluation of conversion efficiency to active metabolites would be helpful for selecting ideal prodrugs as well as appropriate animals for in vivo PK studies." @default.
• W3005412519 created "2020-02-14" @default.
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• W3005412519 date "2020-05-01" @default.
• W3005412519 modified "2023-09-27" @default.
• W3005412519 title "A Novel Systematic Approach for Selection of Prodrugs Designed to Improve Oral Absorption" @default.
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• W3005412519 doi "https://doi.org/10.1016/j.xphs.2020.01.028" @default.
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