Yousef Malaz, Yáñez Jaime A, Löbenberg Raimar, Davies Neal M
Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, AB T6G 2E1, Canada.
Escuela de Posgrado, Universidad Internacional Iberoamericana, Campeche 24560, Mexico.
Biomedicines. 2024 Aug 13;12(8):1843. doi: 10.3390/biomedicines12081843.
The law of superposition underpins first-order linear pharmacokinetic relationships. Most drugs, therefore, after a single dose can be described by first-order or linear processes, which can be superposed to understand multiple-dose regimen behavior. However, there are a number of situations where drugs could display behaviors after multiple dosing that leads to capacity-limited or saturation non-linear kinetics and the law of superposition is overruled. This review presents a practical guide to understand the equations and calculations for single and multiple-dosing regimens after intravenous and oral administration. It also provides the pharmaceutical basis for saturation in ADME processes and the consequent changes in the area under the concentration-time curve, which represents drug exposure that can lead to the modulation of efficacy and/or toxic effects. The pharmacokineticist must implicitly understand the principles of superposition, which are a central tenet of drug behavior and disposition during drug development.
叠加原理是一级线性药代动力学关系的基础。因此，大多数药物在单次给药后可用一级或线性过程来描述，这些过程可以叠加起来以理解多剂量给药方案的行为。然而，在许多情况下，药物在多次给药后可能会表现出导致容量受限或饱和非线性动力学的行为，叠加原理不再适用。本综述提供了一份实用指南，以理解静脉注射和口服给药后单剂量和多剂量给药方案的方程和计算。它还提供了药物在吸收、分布、代谢和排泄（ADME）过程中饱和的药学基础，以及由此导致的浓度-时间曲线下面积的变化，该面积代表药物暴露，可导致疗效和/或毒性作用的调节。药代动力学家必须深入理解叠加原理，这是药物研发过程中药物行为和处置的核心原则。
