Absorption properties and P-glycoprotein activity of modified Caco-2 cell lines.

Caco-2 cell line is extensively used as an in vitro model in studying small intestinal absorption but it lacks proper expression of efflux pumps and cytochrome P450 enzymes that are involved in absorption and first pass metabolism of drugs. We created two novel Caco-2 cell lines expressing orphan nuclear receptors pregnane X receptor and constitutive androstane receptor that regulate many genes involved in xenobiotic metabolism. We conducted a systematic study on expression of some metabolic genes, P-glycoprotein activity and absorption properties of several drugs with these new cell lines and previously described modified Caco-2 cell lines (MDR1 transfection, vincristine treatment and 1alpha,25-dihydroxyvitamin D3 treatment).

Characterization of Caco-2 cell monolayer drug transport properties by cassette dosing using UV/fluorescence HPLC.

Cassette dosing is commonly used in pharmacokinetic studies to decrease time, labor and expenditures. Cassette dosing (having several compounds in a mixture) has been used to screen in vitro permeabilities in Caco-2 cell monolayers. The cassette dosing method has accelerated both transport experiments and sample analyses, which are both part of Caco-2 permeability screening.