Insights into the cellular pharmacokinetics and pharmacodynamics of thiopurine antimetabolites in a model of human intestinal cells

Thiopurines, immunomodulating drugs used in the management of different chronic autoimmune conditions and as anti-leukemic agents, may exert some cases gastrointestinal toxicity. Moreover, since these agents are administered orally, they absorbed across tract epithelium. On premises, cellular molecular events occurring intestinal cells be important to understand thiopurine effects. However, quantitative information on biotransformation thiopurines tissues is still limited. To shed light processes specific tissue, this study metabolites concentrations were analyzed by an vitro model human healthy colon, HCEC cell line, upon exposure cytotoxic azathioprine or mercaptopurine; investigation was carried out using innovative mass spectrometry method, that allowed simultaneous quantification 11 mono-, di-, triphosphate thionucleotides. Among evaluated, TIMP, TGMP, TGDP, TGTP, MeTIMP, MeTIDP MeTITP detectable treated with mercaptopurine, considering two incubation times before addition (4 48 h). Different associations between cytotoxicity detected. In particular, dependent TGTP after 4 h thiopurines. This indication that, association metabolite activity vitro, short growth treatment should used. for first time our findings highlight strong correlation pharmacokinetics suggesting could a suitable studying cytotoxicity.