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Updated: Jun 9, 2025

Mass Spectrometry and Luminogenic-based Approaches to Characterize Phase I Metabolic Competency of In Vitro Cell Cultures
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Mass Spectrometry and Luminogenic-based Approaches to Characterize Phase I Metabolic Competency of In Vitro Cell Cultures

Published on: March 28, 2017

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建立一个基于生理学的阿尔德海德氧化酶和双阿尔德海德氧化酶-CYP基质的药理动力学框架

Nihan Izat1, Jayaprakasam Bolleddula2, Pasquale Carione3

  • 1Centre for Applied Pharmacokinetic Research, The University of Manchester, Manchester, UK.

CPT: pharmacometrics & systems pharmacology
|October 24, 2024
PubMed
概括

基于生理学上的药理动力学 (PBPK) 建模改善了阿尔德海德氧化酶 (AO) 和细胞染色体P450s (CYPs) 通过药物清除的预测. 该框架有助于评估双AO-CYP基质的临床药物相互作用风险.

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Author Spotlight: Developing a Simple and Robust Hepatic Model for Pharmacological and Toxicological Applications

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Application of AlDeSense to Stratify Ovarian Cancer Cells Based on Aldehyde Dehydrogenase 1A1 Activity09:59

Application of AlDeSense to Stratify Ovarian Cancer Cells Based on Aldehyde Dehydrogenase 1A1 Activity

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Phase I Reactions: Oxidation of Aliphatic and Aromatic Carbon-Containing Systems01:19

Phase I Reactions: Oxidation of Aliphatic and Aromatic Carbon-Containing Systems

Phase I biotransformation reactions are integral to drug metabolism, predominantly involving oxidative, reductive, and hydrolytic transformations. Chief among these are oxidative reactions, which enhance the hydrophilicity of xenobiotics and introduce polar functional groups to facilitate their elimination from the body.
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Drug Metabolism: Phase I Reactions01:17

Drug Metabolism: Phase I Reactions

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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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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Oxidations of Aldehydes and Ketones to Carboxylic Acids01:15

Oxidations of Aldehydes and Ketones to Carboxylic Acids

Oxidation of aldehydes and ketones results in the formation of carboxylic acids. Aldehydes, bearing hydrogen next to the carbonyl group, are easily oxidized compared to ketones. This is because an aldehydic proton can easily be abstracted during oxidation.
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Phase I biotransformation, or functionalization, is a crucial chemical process that converts drugs and other xenobiotics into more water-soluble forms, facilitating expulsion from the body. It involves oxidative, reductive, and hydrolytic reactions that add or unveil polar functional groups on lipophilic substrates. Key players in phase I reactions are the mixed-function oxidases. Situated in liver cell microsomes, these enzymes predominantly carry out drug metabolism. They require molecular...
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Oxidation of Alcohols02:37

Oxidation of Alcohols

In this lesson, the oxidation of alcohols is discussed in depth. The various reagents used for oxidation of primary and secondary alcohols are detailed, and their mechanism of action is provided.
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