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Tacrolimus metabotropic diagnostic marker and application thereof

A tacrolimus and metabolite technology, applied in the field of diagnostic markers of tacrolimus metabolizer, can solve problems such as adverse consequences, narrow safety range, and difficulty in formulating a fixed dose of tacrolimus for liver transplant patients , to achieve high accuracy

Inactive Publication Date: 2017-02-15
SHANGHAI FIRST PEOPLES HOSPITAL
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  • Abstract
  • Description
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AI Technical Summary

Problems solved by technology

Due to the obvious inter-individual and intra-individual differences in the absorption distribution of tacrolimus, the therapeutic index is low, and the safety range is narrow. Although the dose is adjusted according to the plasma trough concentration and clinical manifestations, the plasma trough concentration is controlled within the therapeutic window. However, it is still difficult to avoid acute and chronic rejection, tacrolimus poisoning after organ transplantation, and even lead to the serious consequences of early loss of function of the transplanted organ, and clinically often encounter different liver transplant recipients with the same body weight and the same dosage. The plasma trough concentration of tacrolimus varies greatly
For a long time, in daily clinical work, it is difficult to formulate a fixed dose of tacrolimus that is suitable for all liver transplant patients. Excessive or insufficient will bring serious adverse consequences

Method used

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  • Tacrolimus metabotropic diagnostic marker and application thereof
  • Tacrolimus metabotropic diagnostic marker and application thereof
  • Tacrolimus metabotropic diagnostic marker and application thereof

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Embodiment

[0031] 1. General Information

[0032] A total of 170 patients who underwent liver transplantation in Shanghai First People's Hospital from July 2007 to March 2012 were collected. Among them, there were 141 males and 29 females. Age (46.8±9.0) years old. Body mass (68.0±11.5) kg. 170 pairs of donor and recipient liver tissues were collected and stored in a -80°C low-temperature refrigerator for later use. All patients received tacrolimus (FK506) + mycophenolate mofetil (MMF) + glucocorticoid immunotherapy regimen after surgery. FK506 began to be used on the second day after the operation, the initial dose was 0.05-0.10mg / (kg·d), the daily dose was divided into two doses in the morning and evening on average, and the drug concentration was monitored, and the drug was gradually adjusted according to the results of the blood drug concentration The dosage is to maintain the blood drug concentration at 7-10ng / L one month after operation.

[0033] 2. Determination of whole blood...

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Abstract

The invention relates to a metabotropic diagnosis kit used for detecting tacrolimus. The diagnosis kit comprises a reagent for detecting gene CYP3A4 rs2242480 SNP loci, a reagent for detecting gene CYP3A5 rs776746 SNP loci, and a reagent for detecting the total bilirubin content. The current clinical dosage of tacrolimus is determined according to the weight of patients, and different dosages of tacrolimus are needed for treatment so that different genotype patients can have the same target plasma concentration. By testing single nucleotide polymorphism (SNP) and clinical biochemical indicators of 170 pairs of liver transplantation donor CYP3A5 rs776746 loci and liver transplantation receptor CYP3A4 rs2242480 loci, the relation with tacrolimus metabolism is discussed, and the basis is provided for individualized drug administration of clinical liver transplantation patients.

Description

technical field [0001] The invention relates to the technical field of molecular biology and nucleotide detection, in particular to a diagnostic marker of tacrolimus metabolism and its application. Background technique [0002] In recent years, due to the innovation of modern liver transplantation surgical techniques, immunosuppressants, and donor liver acquisition and preservation techniques, liver transplantation has made great progress and has become a standard method for the treatment of end-stage liver diseases, which has significantly improved the quality of life of patients. Calmodulin phosphatase inhibitors (CNIs): cyclosporine A (CsA) and tacrolimus (Tac) are currently the basic immunosuppressive drugs for anti-rejection therapy after liver transplantation. Tacrolimus (Tac) is a potent immunosuppressant with a macrolide structure. It was developed from the fermentation product by Fujisawa Pharmaceutical in Japan in 1982 and extracted from the broth medium of soil fu...

Claims

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Application Information

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IPC IPC(8): C12Q1/68
CPCC12Q1/6883C12Q2600/106C12Q2600/156
Inventor 樊军卫刘园彭志海钟林孙红成顾海涛郭峰张滔
Owner SHANGHAI FIRST PEOPLES HOSPITAL
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