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Method for detecting inhibitory effect of drug on human liver cytochrome P450

A cytochrome and inhibitory technology, applied in the field of medical testing, can solve the problems of impractical and impractical testing of genetic polymorphisms, achieve significant social and economic benefits, reduce interactions, and avoid interactions Effect

Inactive Publication Date: 2012-12-12
SHANGHAI SIXTH PEOPLES HOSPITAL
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Metabolic drug interactions account for a large proportion of adverse drug reactions. However, at present, the detection of genetic polymorphisms in related genes cannot be generally carried out for drug users. Gene chips are used to test the entire human gene to find polymorphisms related to drug efficacy. The practice of spotting is also impractical. In order to reduce or avoid the occurrence of metabolic drug interactions, the easiest and most feasible method is to choose drugs reasonably. At present, metabolic drug interactions have become a necessary item for new drug declaration. Therefore, Investigate the inhibitory effect of drugs on human cytochrome P450, and carry out prospective early prevention, which can avoid the side effects or curative effect reduction caused by drug interactions, which is very important for drug screening and clinical guidance of drug use.

Method used

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  • Method for detecting inhibitory effect of drug on human liver cytochrome P450
  • Method for detecting inhibitory effect of drug on human liver cytochrome P450
  • Method for detecting inhibitory effect of drug on human liver cytochrome P450

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0035] Phenacetin was selected as the probe drug of CYP1A2.

[0036] An in vitro incubation system was established; different concentrations of test drugs, probe drugs and human liver microsomes were co-incubated.

[0037]Incubation system: liver microsome in vitro incubation system with a final volume of 150 μl includes a certain concentration of microsomes, phosphate buffer (100 mM) with a pH of 7.4, MgCl 2 Solution (3mM), different probe drugs corresponding to each subtype and different concentrations of test drugs.

[0038] Pre-incubate in a water bath at 37°C for 5 min, add G-6-P (5mM), NADP + (1mM) and G-6-PDH (1unit / mL) NADPH regeneration system, start the reaction, incubate for a specific time, and control the volume concentration of the organic solvent within 1% of the entire incubation system. The protein concentration and incubation time are shown in Table 1.

[0039] After the incubation reaction was terminated, the reaction was terminated with glacial acetonitr...

Embodiment 2

[0042] Diclofenac was selected as the probe drug of CYP2C9.

[0043] An in vitro incubation system was established; different concentrations of test drugs, probe drugs and human liver microsomes were co-incubated.

[0044] Incubation system: liver microsome in vitro incubation system with a final volume of 150 μl includes a certain concentration of microsomes, phosphate buffer (100 mM) with a pH of 7.4, MgCl 2 Solution (3mM), different probe drugs corresponding to each subtype and different concentrations of test drugs.

[0045] Pre-incubate in a water bath at 37°C for 5 min, add G-6-P (5mM), NADP + (1mM) and G-6-PDH (1unit / mL) NADPH regeneration system, start the reaction, incubate for a specific time, and control the volume concentration of the organic solvent within 1% of the entire incubation system. The protein concentration and incubation time are shown in Table 1.

[0046] After the incubation reaction was terminated, the reaction was terminated with glacial acetonit...

Embodiment 3

[0049] s-(+) mephenytoin was selected as the probe drug of CYP2C19.

[0050] An in vitro incubation system was established; different concentrations of test drugs, probe drugs and human liver microsomes were co-incubated.

[0051] Incubation system: liver microsome in vitro incubation system with a final volume of 150 μl includes a certain concentration of microsomes, phosphate buffer (100 mM) with a pH of 7.4, MgCl 2 Solution (3mM), different probe drugs corresponding to each subtype and different concentrations of test drugs.

[0052] Pre-incubate in a water bath at 37°C for 5 min, add G-6-P (5mM), NADP + (1mM) and G-6-PDH (1unit / mL) NADPH regeneration system, start the reaction, incubate for a specific time, and control the volume concentration of the organic solvent within 1% of the entire incubation system. The protein concentration and incubation time are shown in Table 1.

[0053] After the incubation reaction was terminated, the reaction was terminated with glacial ...

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Abstract

The invention provides a method for detecting the inhibitory effect of a drug on the human liver cytochrome P450. According to the invention, a probe drug, a to-be-detected drug and human liver microsomes containing the cytochrome P450 are subjected to incubation together, then metabolites of the probe drug are detected, and the inhibitory effect of the to-be-detected drug on the cytochrome P450 can be effectively detected; therefore, a convenient method for industrial drug research, development and screening and clinical medication guidance is provided.

Description

technical field [0001] The invention relates to a medicine detection technology, in particular to a method for detecting the inhibitory effect of medicine on human cytochrome P450 (or its subtype). Background technique [0002] Drug interactions are generally divided into pharmacokinetic interactions and pharmacodynamic interactions. Pharmacokinetic interactions can occur in the four stages of absorption, distribution, metabolism, and excretion, among which metabolic interactions have the highest incidence, accounting for about 40% of pharmacokinetic interactions, and have very important clinical significance. The main site of drug metabolism is the liver, and the liver biotransformation depends on various enzyme systems in the microsomes, the most important of which is cytochrome P450 mixed-function oxidase (CYP450 for short). [0003] Cytochrome P450 is the most important drug-metabolizing enzyme in the human body. It is mainly distributed in the liver and participates in...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12Q1/26
Inventor 郭澄韩永龙李丹余奇万丽丽
Owner SHANGHAI SIXTH PEOPLES HOSPITAL
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