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Drug effect estimation method for zidovudine

A technology of zidovudine and pharmacodynamics, applied in the field of pharmacokinetics, can solve the problems of inability to respond well to the effect of zidovudine, large individual differences in curative effect response, toxic and side effects, etc.

Active Publication Date: 2018-11-09
余鹏
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, clinical data show that the curative effect of zidovudine varies greatly among individuals, and severe side effects are prone to occur, such as bone marrow suppression, thrombocytopenia, cardiotoxicity, etc.
In current pharmacokinetic studies, the method for estimating the efficacy of zidovudine is mainly to obtain the plasma concentration of zidovudine and the time of administration by fitting the blood drug concentration at multiple time points after administration. relationship, can not well reflect the effect of zidovudine

Method used

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  • Drug effect estimation method for zidovudine
  • Drug effect estimation method for zidovudine
  • Drug effect estimation method for zidovudine

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0074] First, the peak drug concentration of target cells in volunteers 1.3 hours after administration was obtained: 0.081ng / 10 6 cell, and then get the target cell half-life concentration corresponding to the half-life time of 4 hours: 0.0405ng / 10 6 cell, substituting the data of these two points into the first formula to calculate the metabolic curve of zidovudine in the target cell:

[0075] C 2 =6844×e -0.5t +177×e -0.5t (C 1 t×e -0.5t -0.5C 1 × e -0.5t )

[0076] where k ab Take 1, k ba +k 0 Take 0.5, C can be obtained by software 1 =-7369e -2.77t +8825e -1.72t +2039e -0.29t , calculated as Figure 4 Metabolism curve of zidovudine triphosphate compound in target cells shown in a.

Embodiment 2

[0078] First obtain the peak drug concentration of target cells in volunteers 1.3 hours after administration: 0.079ng / 10 6 cell, and then get the target cell half-life concentration corresponding to the half-life time of 4 hours: 0.0395ng / 10 6 cell, substituting the data of these two points into the first formula to calculate the metabolic curve of zidovudine in the target cell:

[0079] C 2 =8349×e -0.5t +143×e -0.5t (C 1 t×e -0.5t -0.5C 1 × e -0.5t )

[0080] where k ab Take 1, k ba +k 0 Take 0.5, C1=-6243 can be obtained by software e -3.79t +7965 e -2.21t +2897e -0.401t , calculated as Figure 5 Metabolism curve of zidovudine triphosphate compound in target cells shown in a.

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Abstract

The invention relates to a drug effect estimation method for zidovudine. The method comprises the following steps of acquiring target cell drug peak concentration of the zidovudine, and obtaining target cell half-life concentration according to the target cell drug peak concentration; obtaining a relation between target cell drug concentration and drug administration time of the zidovudine according to target cell time to peak, the target cell drug peak concentration, target cell half-life time, the target cell half-life concentration and a first formula, wherein the first formula is (formula); and obtaining a relation between the target cell drug concentration and the drug administration time of a zidovudine phosphorylated product after 0.4 to 0.6 hour according to the relation between the target cell drug concentration and the drug administration time of the zidovudine. In this way, the drug effect of the zidovudine in target cells can be estimated by only acquiring the data of the target cell drug peak concentration.

Description

technical field [0001] The invention relates to the field of pharmacokinetics, in particular to a method for estimating the efficacy of zidovudine. Background technique [0002] Zidovudine (AZT) is a synthetic thymidine antiviral drug and has become the first drug approved for the treatment of acquired immunodeficiency syndrome (AIDS). Zidovudine is a water-soluble molecule that requires a specific transfer protein to enter the cell, and then is phosphorylated by the corresponding kinase to become a triphosphate active derivative, and then inhibits the activity of the virus reverse transcriptase (reverse transcriptase, RT), terminates The extension of the viral DNA chain and the inhibition of viral replication can achieve antiviral effects, which can improve the clinical symptoms of HIV-infected patients and reduce their mortality. However, clinical data show that the curative effect of zidovudine varies greatly among individuals, and severe side effects are prone to occur,...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): G06F19/00G16H70/40G06F17/18
CPCG06F17/18G16H70/40
Inventor 孟凡奇余鹏刘星菱邱朝晖蒋蕾丁尧张可
Owner 余鹏
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