Contribution of Japanese scientists to drug metabolism and disposition

Miki Nakajima1, Hiroshi Yamazaki2, Kouichi Yoshinari3

  • 1Drug Metabolism and Toxicology, Faculty of Pharmaceutical Sciences, Kanazawa University, Kanazawa, Japan; WPI Nano Life Science Institute, Kanazawa University, Kanazawa, Japan.

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A drug's physicochemical properties fundamentally influence its metabolism. For instance, a drug's molecular size and shape critically determine its interaction with enzymes and transporters — larger drugs may face difficulty reaching enzyme active sites, altering their metabolic pathways. The pKa of a drug, which establishes its ionization state, can impact its solubility and absorption, thereby influencing metabolism.
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Biological factors significantly impact drug metabolism, influencing drug clearance, efficacy, and potential toxicity.
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A phase I reaction is a biochemical process that introduces a functionally reactive polar group to a substance. This transformation predominantly occurs in the liver, facilitated by the cytochrome P450 system of hemoproteins situated in the lipophilic endoplasmic reticulum of cells. The metabolite generated through this process can have varying polarities. If it is sufficiently polar, it can be easily excreted in the urine due to its water compatibility. However, if the metabolite is nonpolar,...
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