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关于将双米氏方程拟合到动力学数据的困难。

On the difficulties of fitting the double Michaelis-Menten equation to kinetic data.

作者信息

Bates J H, Bates D A, Mackillop W

机构信息

Meakins-Christie Laboratories, McGill University, Montreal, Quebec, Canada.

出版信息

J Theor Biol. 1987 Mar 21;125(2):237-41. doi: 10.1016/s0022-5193(87)80044-9.

DOI:10.1016/s0022-5193(87)80044-9
PMID:3657211
Abstract

The double Michaelis-Menten equation describes the reaction kinetics of two independent, saturable uptake mechanisms. The use of this equation to describe drug uptake has been reported several times in the literature, and several methods have been published to fit the equation to data. So far, however, confidence intervals on the fitted kinetic parameters have not been provided. We present a grid-search method for fitting the double Michaelis-Menten equation to kinetic uptake data, and a Monte-Carlo procedure for estimating confidence intervals on the fitted parameters. We show that the fitting problem is extremely ill-conditioned, and that very accurate data are required before any confidence can be placed in the fitted parameters.

摘要

双米氏方程描述了两种独立的、可饱和摄取机制的反应动力学。文献中已多次报道使用该方程来描述药物摄取情况,并且已经发表了几种将该方程与数据拟合的方法。然而,到目前为止,尚未提供拟合动力学参数的置信区间。我们提出了一种将双米氏方程与动力学摄取数据拟合的网格搜索方法,以及一种用于估计拟合参数置信区间的蒙特卡罗程序。我们表明,拟合问题的条件极差,在对拟合参数有任何信心之前,需要非常精确的数据。

相似文献

1
On the difficulties of fitting the double Michaelis-Menten equation to kinetic data.关于将双米氏方程拟合到动力学数据的困难。
J Theor Biol. 1987 Mar 21;125(2):237-41. doi: 10.1016/s0022-5193(87)80044-9.
2
Application of modified Michaelis - Menten equations for determination of enzyme inducing and inhibiting drugs.改良米氏方程在酶诱导和抑制药物测定中的应用。
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First-pass effect: nonlinear concept comprising an explicit solution of integrated Michaelis-Menten equation.首过效应:非线性概念,包含米氏方程积分的显式解。
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Integrated equation to evaluate accumulation profiles of drugs eliminated by Michaelis-Menten kinetics.用于评估通过米氏动力学消除的药物蓄积曲线的综合方程。
J Pharmacokinet Biopharm. 1979 Apr;7(2):227-32. doi: 10.1007/BF01059740.
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Computational problems of compartment models with Michaelis-Menten-type elimination.具有米氏消除型的房室模型的计算问题。
J Pharm Sci. 1981 Jul;70(7):733-7. doi: 10.1002/jps.2600700706.
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Kinetic parameter estimation by numerical algorithms and multiple linear regression: application to pharmacokinetics.通过数值算法和多元线性回归进行动力学参数估计:在药代动力学中的应用。
J Pharm Sci. 1979 Sep;68(9):1120-4. doi: 10.1002/jps.2600680916.
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Computation of the explicit solution to the Michaelis-Menten equation.米氏方程显式解的计算。
J Pharmacokinet Biopharm. 1983 Dec;11(6):641-57. doi: 10.1007/BF01059062.
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Exact and approximate solutions for the decades-old Michaelis-Menten equation: Progress-curve analysis through integrated rate equations.有着数十年历史的米氏方程的精确解和近似解:通过积分速率方程进行的进程曲线分析。
Biochem Mol Biol Educ. 2011 Mar-Apr;39(2):117-25. doi: 10.1002/bmb.20479.
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Comparison of various estimation methods for the parameters of Michaelis-Menten equation based on elimination kinetic simulation data.基于消除动力学模拟数据的米氏方程参数的各种估计方法比较
Transl Clin Pharmacol. 2018 Mar;26(1):39-47. doi: 10.12793/tcp.2018.26.1.39. Epub 2018 Mar 16.
10
Michaelis-Menten metabolite formation kinetics: equations relating area under the curve and metabolite recovery to the administered dose.米氏代谢物形成动力学:将曲线下面积和代谢物回收率与给药剂量相关联的方程式。
J Pharm Sci. 1990 Oct;79(10):902-6. doi: 10.1002/jps.2600791012.

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2
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The effect of hyperthermia in combination with melphalan on drug-sensitive and drug-resistant CHO cells in vitro.热疗联合美法仑对体外培养的药物敏感和耐药CHO细胞的作用。
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Testing and characterizing enzymes and membrane-bound carrier proteins acting on amphipathic ligands in the presence of bilayer membrane material and soluble binding protein. Application to the uptake of oleate into isolated cells.在存在双层膜材料和可溶性结合蛋白的情况下,对作用于两亲性配体的酶和膜结合载体蛋白进行检测和表征。应用于油酸进入分离细胞的摄取过程。
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