Is active transport accounted for?
A. It is accounted for indirectly because we use Caco-2 permeability which does implicitly include the effect of active transport. In most cases in vivo, concentrations in the small intestine will be high – in the millimolar range, so you will be in a linear region – any non-linearity caused by active transport will be negligible. Therefore, an estimate of total permeability, comprising passive and active components, which you can obtain from Caco-2, will be useful. The sensitivity analysis for permeability should give you some reasonable guidance on whether active transport – insofar as it affects total permeability – will affect absorption. The evidence is that this works surprisingly well. See our validation report here.