Where the Science Still Has Gaps Several questions remain unresolved: optimal dosing for therapeutic applications long-term systemic safety standardized clinical protocols large randomized human trials These gaps highlight the difference between promising experimental science and established clinical practice
Overall, comparison of reported K p,brain, AUC u,brain /AUC u,plasma and K p,uu,brain values for released parent drug after prodrug dosing and drug itself (Table II) revealed significant improvement of brain delivery extent after administration of the following prodruds/derivatives: L-lysine-methotrexate conjugate in mice (117), lysine derivative of ketoprofen in rats (112), phenylalanine derivatives of ketoprofen in mice (79), venlafaxine-thiamine disulfide-glucose prodrug in mice (144), glucose prodrug of ibuprofen in mice (145), ascorbic acid derivatives of ibuprofen in mice (145, 147)
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The triple mutant clt1clt2clt3 is deficient in the transport of EC and glutathione from the plastid to the cytosol and shows lower cytosolic and higher plastidic glutathione levels 57 , but did not exhibit any difference in root length compared to WT when exposed to AITC
