Sun H, Chow M S
Drug Information Center, Hartford Hospital, CT, USA.
Drug Metab Dispos. 1995 Apr;23(4):449-54.
Assuming a one-compartment model and first-order processes for drug release, absorption, and elimination, a new equation to describe the fraction of drug to be absorbed (1-Ft) for a sustained-release product is derived. Based on this equation, when In(1-Ft) vs. time is plotted, the slopes yield the drug release rate constant (Kr), the drug absorption rate constant (Ka), and two intercepts that are a mixed function of Ka, Kr, and the fraction of sustained-release (Fs). The accuracy of this equation to generate pharmacokinetic parameters, such as Ka, Kr, Fs, and the bioavailability-volume of distribution ratio (FD/V) was tested by fitting this equation to multiple simulated plasma concentration-time data (5 sets errorless and 75 sets errant data). The absolute percentage error of Ka and FD/V estimated by this equation is much less than that of traditional polyexponential equation, whereas the absolute percentage error of Kr estimated by this equation is statistically significantly less than that of traditional polyexponential equation. Furthermore, with this equation, it is easier to estimate Fs than with traditional equation. An application of this equation in generating these parameters is illustrated for a quinidine sustained-release dosage form-quinidex.
假设采用单室模型以及药物释放、吸收和消除的一级过程，推导出了一个用于描述缓释产品中药物吸收分数（1 - Ft）的新方程。基于此方程，当绘制ln(1 - Ft)对时间的曲线时，斜率可得出药物释放速率常数（Kr）、药物吸收速率常数（Ka）以及两个截距，这两个截距是Ka、Kr和缓释分数（Fs）的混合函数。通过将该方程拟合到多个模拟的血浆浓度 - 时间数据（5组无误差数据和75组有误差数据），测试了该方程生成药代动力学参数（如Ka、Kr、Fs以及生物利用度 - 分布容积比（FD/V））的准确性。该方程估计的Ka和FD/V的绝对百分比误差远小于传统的多指数方程，而该方程估计的Kr的绝对百分比误差在统计学上显著小于传统的多指数方程。此外，使用该方程比使用传统方程更容易估计Fs。以奎尼丁缓释剂型 - 硫酸奎尼丁为例说明了该方程在生成这些参数方面的应用。
