Abstract: The present invention provides a method of using a physiologically-based pharmacokinetic model to select a prodrug molecule (NO—X) comprising a therapeutic agent X (e.g. nonsteroidal anti-inflammatory drug, (NSAID)) and an appropriate nitric oxide donor NO. The NSAID can be a non-selective or selective cyclooxygenase inhibitor or other biocompatible compound comprising a carboxyl group. The pharmacokinetic model uses in vitro and/or in silico data to estimate an optimal set of parameters that can predict whether a particular NO—X candidate is capable of producing desirable therapeutic effects, e.g. enhanced anti-inflammatory activity, reduced intestinal, cardiac and renal toxicity. Accordingly, the present invention can greatly enhance proper selection of an appropriate candidate for drug development, thereby minimizing development time and conserving costs.

Abstract: In one aspect, the invention provides cell cultures and culture conditions that facilitate the establishment of an intestinal epithelial cell culture that has characteristics of the intestinal epithelium, such as: transepithelial electrical resistance, enzyme expression and microvilli morphology. Cell cultures of the invention may use fatty acids such as sodium butyrate and kinase modulators such as 2-{1-[3-(amidinothio)propyl]-1H-indol-3-yl}-3-(1-meethylindol-3-yl)-maleimide methanesulfonate.