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  Mechanisms of CYP450 Inhibition: Understanding Drug-Drug Interactions Due to Mechanism-Based Inhibition in Clinical Practice. (2025). Pharmaceutics, 12(5), 463. https://doi.org/10.3390/pharmaceutics12050463 相关领域
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Zeta电位
固体脂质纳米粒
透皮
化学
刺激
分散性
结晶度
色谱法
粒径
溶剂
纳米颗粒
有机化学
材料科学
药物输送
药理学
生物化学
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物理化学
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Abstract Cytochrome P450 (CYP)-mediated metabolism is the most important mechanism involved in drug clearance, drug-drug interactions, and adverse drug reactions. Mechanism-based inhibition (MBI), also known as time-dependent inhibition (TDI), is a common cause of clinically significant drug interactions and is associated with the formation of reactive metabolites. MBI is characterized by time-, concentration-, and NADPH-dependent inactivation of CYPs, which occurs when a parent drug is bioactivated by the CYP enzyme into a reactive intermediate that then covalently binds to the heme moiety or apoprotein, resulting in irreversible enzyme inactivation. At low substrate concentrations, metabolite formation increases with increasing substrate concentration because enzyme inactivation is minimal. However, at higher substrate concentrations, extensive formation of reactive intermediates leads to rapid and near-complete inactivation of the available |
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