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Modeling transportation of efavirenz: inference on possibility of mixed modes of transportation and kinetic solubility

机译:依法韦仑的运输模拟:推断混合运输方式和动力学溶解度的可能性

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摘要

Understanding drug transportation mechanisms in the human body is of paramount importance in modeling Pharmacokinetic-Pharmacodynamic relationships. This work gives a novel general model of efavirenz transportation projections based on concentrations simulated from patients on a dose of 600 mg. The work puts forward a proposition that transportation can wholly be modeled by concentration and time in a uniform volumetric space. Furthermore, movement entities are used to inform the state of “kinetic solubility” of a solution. There is use of Ricker's model, and forms of the Hill's equation in modeling transportation. Characterization on the movement rates of solution particle are suggested in relation to advection rate of solution particle. At turning points on the transportation rate of solution particle vs. concentration curve, a suggestion of possibly change of dominance in the mode of transportation and saturation is made. There are four movement rates postulated at primary micro-level transportation, that are attributed to convection, diffusion [passive transportation (EI)] and energy dependent system transportation (ED) in relation to advection. Furthermore, a new parameter is introduced which is defined as an advection rate constant of solution particle. It is postulated to be dependent on two rate constants of solution particle, that is a convection rate constant of solution particle and a saturable transportation rate constant of solution particle. At secondary micro-level transportation, the results show convection as sum of advection and saturable transportation. The kinetics of dissolution of efavirenz in the solution space is postulated. Relatively, a good level of kinetics of dissolution is projected in the concentration region 0 − 32.82 μg/ml.
机译:在建模药代动力学与药效关系时,了解人体中的药物运输机制至关重要。这项工作基于患者剂量为600 mg时模拟的浓度,给出了依非韦伦传输预测的新型通用模型。这项工作提出了一个建议,即运输可以完全由浓度和时间在一个统一的体积空间中建模。此外,运动实体用于告知溶液的“动力学溶解度”状态。在对运输进行建模时,使用了Ricker模型和Hill方程的形式。提出了关于溶液颗粒的对流速率的表征。在溶液颗粒的传输速率与浓度曲线的转折点上,提出了在传输模式和饱和模式下可能会改变主导地位的建议。在主要的微观水平运输中假设有四个运动速率,这归因于对流,对流,扩散[被动运输(EI)]和能量依赖系统运输(ED)。此外,引入了新的参数,其被定义为溶液颗粒的对流速率常数。假定它取决于溶液颗粒的两个速率常数,即溶液颗粒的对流速率常数和溶液颗粒的饱和传输速率常数。在二次微层运输中,结果表明对流是对流与饱和运输的总和。推测依非韦伦在溶液空间的溶解动力学。相对地,在0-32.82μg/ ml的浓度范围内,有较高的溶解动力学水平。

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