• Both MetMaxTM and Intact Human Hepatocytes yielded data comparable to clinical systemic clearance One interesting finding was that MetMaxTM hepatocytes were superior to pooled cryopreserved human hepatocytes in the… Click to show full abstract
• Both MetMaxTM and Intact Human Hepatocytes yielded data comparable to clinical systemic clearance One interesting finding was that MetMaxTM hepatocytes were superior to pooled cryopreserved human hepatocytes in the evaluation of afatinib, a drug that is known to be subjected to FMO and GST. The excellent in vitro-in vivo correlation plus the simplicity of the application of MetMaxTM hepatocytes (storage in -80 deg. C, thaw-and-use (elimination of centrifugation and cell counting), are features supporting routine application of this novel experimental system in the high throughput screening of hepatic metabolic stability • Screening for metabolic stability is routinely performed in drug development • Metabolic stability screening with human hepatocytes provide a more comprehensive evaluation than that with human liver microsomes due to the presence of all key drug metabolizing enzyme pathways, especially phase 2 conjugative metabolism • High throughput screening with human hepatocytes is challenged by the sensitivity of the cells to robotic manipulation • MetMaxTM human hepatocytes, a novel in vitro drug metabolism system, with the complete drug metabolizing enzyme pathways and the robustness and ease-of-use of liver microsomes, represent an ideal systme for metabolic stability screening. • Our study compares results of metabolic stability screening with drugs with known in vivo hepatic clearance between pooled donor human hepatocytes and MetMaxTM pooled donor human hepatocytes
               
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