Veng-Pedersen P
J Pharm Sci. 1985 Jan;74(1):90-3. doi: 10.1002/jps.2600740125.
Current methods of evaluating the bioavailability of drugs with nonlinear disposition kinetics are based on specific pharmacokinetic models in contrast to the more rational model independent (structureless) area under the curve (AUC) and deconvolution methods used in linear pharmacokinetics. A novel method of evaluating bioavailability is presented which applies to any nonlinear type of drug elimination, but is limited to drugs with a distribution phase which is short relative to the elimination phase. The method applies to drugs with autonomic disposition characterized by a rate of decline in the systemic drug level in the absence of drug input which depends only on the drug level, i.e., dC/dt = -q(C), where q can be any function dependent only on C and constant kinetic parameters. It is shown that the disposition function q(C) can be evaluated in an empirical fashion from elimination-phase data and that this function can be used to calculate the absolute bioavailability of autonomic, nonlinear drugs. Some preliminary results are presented to demonstrate the procedures involved in applying the method.
与线性药代动力学中使用的更合理的非模型依赖（无结构）曲线下面积（AUC）和反卷积方法相反，目前评估具有非线性处置动力学的药物生物利用度的方法是基于特定的药代动力学模型。本文提出了一种评估生物利用度的新方法，该方法适用于任何非线性类型的药物消除，但仅限于分布相相对于消除相较短的药物。该方法适用于具有自主处置特征的药物，其在无药物输入时全身药物水平的下降速率仅取决于药物水平，即dC/dt = -q(C)，其中q可以是仅依赖于C和恒定动力学参数的任何函数。结果表明，处置函数q(C)可以根据消除相数据以经验方式进行评估，并且该函数可用于计算自主、非线性药物的绝对生物利用度。给出了一些初步结果以证明应用该方法所涉及的步骤。
