Cell culture model for drug bioavailability

Abstract

A model utilizing cells for assessing oral bioavailability and potential drug-drug interactions of pharmacological agents is described. The model subjects cells (e.g., Caco-2 cells) to conditions that result in reliable expression of catalytically-active CYP3A4 at levels that appear to be comparable to levels present in mature enterocytes. These conditions include plating of selected clones on an extracellular matrix, exposure to 1.alpha.,25-(OH).sub.2 -D.sub.3 for a defined period of time, and the presence of serum in the medium. The model is useful for defining the role of CYP3A4 in limiting the oral bioavailability of many pharmacological agents and in drug-drug interactions involving CYP3A4 substrates that are believed to occur largely at the level of the intestine.

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