【摘 要】
：
When evaluating clinical drug-drug interactions (DDI), revealing whether and how the role of the metabolic status in the entire drug disposition in vivo aff
【机 构】
：
Laboratory of Pharmaceutical Resource Discovery, Dalian Institute of Chemical Physics,Chinese Academ
【出 处】
：
2015年第一届药代动力学朝阳论坛
论文部分内容阅读
When evaluating clinical drug-drug interactions (DDI), revealing whether and how the role of the metabolic status in the entire drug disposition in vivo affect DDI risk remains major challenges, due to interference of other non-metabolic factor including blood flow and protein-binding.Here, we introduced a new parameter At in a reconstructed model to determine the metabolism-dominant duration, which evidently impacted the metabolism-mediated DDI risk.With the novel model, we found that risk of metabolic DDI is correlated with the duration of At.Both substrate concentration and enzymatic capacity are determinants of At: an increase in substrate concentration increases At, whereas an enhancement in enzymatic capacity decreases At.Additionally, the At model could explain why DDI risk is elevated in the elderly and in patients with poor metabolic capacity, and also resolve the discrepancy between in vitro prediction by I/Ki ratio and clinical outcomes.
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