School of Pharmacy, University of Athens, Panepistimiopolis, Athens, Greece.
Eur J Pharm Sci. 2010 Oct 9;41(2):299-304. doi: 10.1016/j.ejps.2010.06.015. Epub 2010 Jul 3.
Most correlations between in vitro and in vivo data (IVIVC) rely on linear relationships. However, non-linear IVIVC can be also observed, justified and validated. The purpose of the present work was the development of a methodology for power law IVIVC, which mirror power law kinetics under in vitro and in vivo conditions. Fractional calculus was used to justify power law kinetics for zero-order processes in disordered media. Power law kinetics was observed in a large number of in vitro data sets. When "zero-order" release and absorption is considered in terms of fractional calculus the following power law IVIVC between the fraction released F(r) and the fraction absorbed F(a), is obtained: F(a)=microF(r)(lambda)-beta, where mu is a constant related to the rate constants and the orders of the release/absorption kinetics, lambda is the ratio of the orders of the kinetics under in vitro and in vivo conditions and beta accounts for a time shift between the in vitro and in vivo processes; We used literature data to develop power law IVIVC and derive estimates for mu, lambda and beta; the simulated pharmacokinetic profiles using the in vitro release data and the IVIVC developed compared well with the actual in vivo data.
大多数体外和体内数据（IVIVC）之间的相关性都依赖于线性关系。然而，也可以观察到、证明和验证非线性 IVIVC。本工作的目的是开发一种用于幂律 IVIVC 的方法，该方法反映了在体外和体内条件下的幂律动力学。分数阶微积分用于证明无序介质中零级过程的幂律动力学。在大量的体外数据集观察到幂律动力学。当从分数阶微积分的角度考虑“零级”释放和吸收时，得到以下分数释放 F(r)和分数吸收 F(a)之间的幂律 IVIVC：F(a)=muF(r)(lambda)-beta，其中 mu 是与释放/吸收动力学的速率常数和阶数相关的常数，lambda 是体外和体内条件下动力学阶数的比值，beta 解释了体外和体内过程之间的时间滞后；我们使用文献数据来开发幂律 IVIVC，并得出 mu、lambda 和 beta 的估计值；使用体外释放数据模拟的药代动力学曲线与开发的 IVIVC 与实际的体内数据非常吻合。
