Evaluation of the appropriate time range for estimating the apparent permeability coefficient (Papp) in a transcellular transport study.
Evaluation of the appropriate time range for estimating the apparent permeability coefficient (Papp) in a transcellular transport study.
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评估跨细胞转运研究中估计表观渗透系数 (Papp) 的适当时间范围。
DOI：
10.1016/j.ijpharm.2015.09.035
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发表时间：
2015
期刊：
影响因子：
--
通讯作者：
K. Ito
中科院分区：
文献类型：
--
作者：
K. Ozeki;M. Kato;Y. Sakurai;M. Ishigai;T. Kudo;K. Ito
在跨细胞转运研究中，化合物的表观渗透系数（Papp）是使用假设在接收侧积累的化合物量与时间成正比的范围来评估的。然而，接收器 (C3) 中化合物浓度的时间曲线通常在达到线性范围之前显示出滞后时间，随后从线性状态变为稳态。在本研究中，计算 C3 时间曲线中的 Papp 所需的线性范围通过 3 室模型进行评估。C3 由具有两个稳态的方程 (C3=A3(1 −e−αt) +B3(1 −e−βt),α>β) 和 3/α<t<0.3/β 时间范围内的简单近似线 (C3=A3−A3×αt) 描述；滞后时间定义为 x 轴的截距，被描述为 1/α。速率常数α受膜通透性清除率和细胞内未结合分数的影响，而β仅受前者影响。本研究中近似的线性范围在 C3 保持在 < 10% 负载浓度的时间间隔内没有统一定义，这被报告为汇条件。 总之，该理论方法表明评估 Papp 的适当时间范围为 3/α<t< 0.3/β。
In a transcellular transport study, the apparent permeability coefficient (Papp) of a compound is evaluated using the range by which the amount of compound accumulated on the receiver side is assumed to be proportional to time. However, the time profile of the concentration of the compound in receiver (C3) often shows a lag time before reaching the linear range and later changes from linear to steady state. In this study, the linear range needed to calculatePappin theC3-time profile was evaluated by a 3-compartment model.C3was described by an equation with two steady states (C3=A3(1 −e−αt) +B3(1 −e−βt),α>β), and by a simple approximate line (C3=A3−A3×αt) in the time range of 3/α<t<0.3/β; the lag time, defined as the interception of thexaxis, was described as 1/α. The rate constant α was affected by the membrane permeability clearance and intracellular unbound fraction, while β was affected only by the former. The linear range that was approximated in the present study was not uniformly defined within the time interval in which C3remains at <10% of the loading concentration, which is reported as the sink condition.In conclusion, this theoretical approach showed that the appropriate time range to evaluatePappwas 3/α<t< 0.3/β.