Commentary to malmborg and ploeger

摘要

I was involved in the current pro-drug project at an early stage, and also acknowledged by authors and former colleagues Malmborg and Ploeger for my input on rate constants and assay selection. Apparently, the project changed direction and prediction methodology after my involvement I was not aware of the new strategy and publication work until the time of publication.It is a good piece of work. However, I found that their Eq. (3) is not applicable for prediction of intestinal k_a as presented in their physiologically-based pharmacokinetic model, and this is likely to have a non-negligible impact on the predictions, outcome, validity and usefulness. In such a set-up Eq. (2) applies. In comparison, the used Eq. (3) gives at least 3-fold higher k_a-values than the proposed Eq. (2). The difference is most pronounced for highly permeable compounds.