【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 affect DDI risk remains major challenges, due t
【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.
其他文献
Drug ADME experiment in humans is a pivotal drug metabolism study in support of drug development and registration.Human ADME study provides information on the exposure of drug related components, excr
There are extensive reports on drug-metabolizing enzymes dysregulation in inflammatory diseases and the distinct regulatory effects of different cvtokines.The present study aimed to depict the changes
Trastuzumab Emtansine(T-DM1, KadcylaTM, Genentech Inc.) is an antibody-drug conjugate(ADC) that received US FDA approval in 2013 for the treatment of human epidermal growth factor receptor 2 (HER2)-po
Herbal medicinal products belong to a main part of complementary and alternative medicine and have worldwide using integrated with conventional medicines for treatment.However, the increasing risk of
LAT1 overexpressed on membrane of various tumor cells, are potential targets for tumor-targeting therapy.This study aimed to develop a LAT1-mediated drug delivery to target chemotherapeutic agents to
Fasiglifam (TAK-875), a selective G-protein-coupled receptor 40 agonist, was developed for the treatment of type 2 diabetes mellitus.However, its clinical development was terminated in phase Ⅲ clinica
Metabolic profile of bile acids was used to evaluate hepatoprotec tion in Nrf2/ARE Oxidation/chemical stress defense pathway caused by Isoliquiritigenin (ISL) based on analysis of 16 bile acids in mic
The furan-containing compounds widely exist in food, herb, synthetic drugs and air pollution, and many of them are toxic.It was proposed that metabolic activation of furan ring was related to their in
To evaluate the effect of the cytochrome P450(CYP) 3A5 polymorphisms on the CYP3A activity and the activation of the clopidogrel in human liver S9 fraction.CYP3A5*3 genotypes of 40 liver tissues were
TPN729MA is a novel selective phosphodiesterase type 5 (PDE5) inhibitor.The preclinical PK of TPN729MA was studied in rats and dogs.Human clearance (CL) values of TPN729MA were predicted from various