Gries J M, Upton R, Huang Y F, Verotta D
Department of Pharmacy and Pharamceutical Chemistry, University of California, San Francisco 94143, USA.
J Pharm Sci. 1996 Apr;85(4):362-8. doi: 10.1021/js950232+.
We describe an explorative data analysis tool which can detect and describe the presence of nonlinearities in multiple dose kinetics studies. The method is nonparametric (i.e. not dependent on modeling assumptions), uses regression to estimate the functions representing the kinetics, and makes the detection of nonlinearity a part of the model selection process. Flexible functions (splines) are used to describe the kinetics corresponding to the lowest given dose, and to describe the (possible) departure of the kinetics corresponding to higher doses from the reference kinetics. The estimated kinetics and departures can be examined to offer possible insight into the nature of the nonlinearity. The methodology is applied to the analysis of meperidine and lidocaine kinetics through the lungs and the heart. We find that the lung kinetics of lidocaine and meperidine are linear. However their myocardial kinetics are complex and nonlinear.
我们描述了一种探索性数据分析工具，它可以在多剂量动力学研究中检测并描述非线性的存在。该方法是非参数的（即不依赖于建模假设），使用回归来估计代表动力学的函数，并将非线性检测作为模型选择过程的一部分。灵活的函数（样条函数）用于描述对应于最低给定剂量的动力学，并描述对应于较高剂量的动力学与参考动力学之间（可能的）偏差。可以检查估计的动力学和偏差，以深入了解非线性的本质。该方法应用于通过肺和心脏对哌替啶和利多卡因动力学的分析。我们发现利多卡因和哌替啶的肺动力学是线性的。然而，它们的心肌动力学是复杂且非线性的。
