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The reduction in AUC after oral administration can result from numerous mechanisms including: pH or bacterial-mediated metabolism of the drug within the GI tract, incomplete drug absorption from the GI tract, metabolism within the GI epithelium (which contains CYP3A4), excretion back into the GI tract by P-glycoprotein in the GI epithelium, hepatic metabolism, or biliary excretion into the GI tract

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Krebs-cycle-deficient hereditary cancer syndromes are defined by defects in homologous-recombination DNA repair