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Updated: Jul 9, 2025

Mass Spectrometry and Luminogenic-based Approaches to Characterize Phase I Metabolic Competency of In Vitro Cell Cultures
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与人类肝脏中CYP2D6表达和活性相关的新型独立转基因和Cis基因变异

Dylan Smith1, Bing He1, Jian Shi1

  • 1Department of Pharmaceutical Sciences, Northeast Ohio Medical University, Rootstown, Ohio (D.S., X.W.); Department of Clinical Pharmacy, University of Michigan, Ann Arbor, Michigan (H.-J.Z.); Department of Computational Medicine and Bioinformatics, University of Michigan Medical School, Ann Arbor, Michigan (B.H.); and Bristol Myers Squibb, Lawrence Township, New Jersey (J.S.).

Drug metabolism and disposition: the biological fate of chemicals
|December 5, 2023
PubMed
概括

研究人员确定了影响细胞染色体P450 2D6 (CYP2D6) 表达和活性的人类肝脏的新型遗传变异. 这些发现有助于解释药物代谢和对CYP2D6基质药物反应的个体间变异性.

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Cell Specific Gene Expression

Multicellular organisms contain a variety of structurally and functionally distinct cell types, but the DNA in all the cells originated from the same parent cells. The differences in the cells can be attributed to the differential gene expression. Liver cells, whose functions include detoxification of blood, production of bile to metabolize fats, and synthesis of proteins essential for metabolism, must express a specific set of genes to perform their functions. Gene expression also varies with...
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Biological factors significantly impact drug metabolism, influencing drug clearance, efficacy, and potential toxicity.
Species differences: Variations in enzyme systems across species can cause disparities in drug metabolism. For instance, humans may metabolize certain drugs faster than rodents, altering therapeutic effects.
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Comparing Copy Number Variations and SNPs02:26

Comparing Copy Number Variations and SNPs

Sequencing of the human genome has opened up several best-kept secrets of the genome. Scientists have identified thousands of genome variations that exist within a population. These variations can be a single nucleotide or a larger chromosomal variation.
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In the liver and bile canaliculi, influx and efflux transporters modification can influence intrinsic clearance. Transporters play a significant role in moving drugs within liver cells. Elaborate models, such as the Biopharmaceutical Classification System (BCS), are essential to relate transporters to drug disposition. This system categorizes drugs into four classes based on solubility and permeability, providing insights into elimination routes and the effects of transporters following oral...
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Physiological Pharmacokinetic Models: Incorporating Hepatic Transporter-Mediated Clearance01:07

Physiological Pharmacokinetic Models: Incorporating Hepatic Transporter-Mediated Clearance

Drug transporters are critical in drug absorption, distribution, and excretion processes. They should be included in physiological-based pharmacokinetic (PBPK) models, which help predict human drug disposition. However, predicting this is challenging during drug development, especially when liver transport is involved. However, with a realistic representation of body transport processes, an accurate model may be possible.
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