Sharma A, Jusko W J
Department of Pharmaceutics, School of Pharmacy, State University of New York at Buffalo, 14260, USA.
Br J Clin Pharmacol. 1998 Mar;45(3):229-39. doi: 10.1046/j.1365-2125.1998.00676.x.
This review describes four basic physiologic indirect pharmacodynamic response (IDR) models which have been proposed to characterize the pharmacodynamics of drugs that act by indirect mechanisms such as inhibition or stimulation of the production or dissipation of factors controlling the measured effect. The principles underlying IDR models and their response patterns are described. The applicability of these basic IDR models to characterize pharmacodynamic responses of diverse drugs such as inhibition of gastric acid secretion by nizatidine and stimulation of MX protein synthesis by interferon alpha-2a is demonstrated. A list of other uses of these models is provided. These models can be readily extended to accommodate additional complexities such as nonstationary or circadian baselines, equilibration delay, depletion or accumulation of a precursor pool, sigmoidicity, or other mechanisms. Indirect response models which have a logical mechanistic basis account for time-delays in many responses and are widely applicable in clinical pharmacology.
本综述描述了四种基本的生理间接药效学反应（IDR）模型，这些模型旨在表征通过间接机制起作用的药物的药效学，例如抑制或刺激控制所测效应的因子的产生或消耗。描述了IDR模型的基本原理及其反应模式。证明了这些基本IDR模型在表征多种药物的药效学反应方面的适用性，如尼扎替丁抑制胃酸分泌和α-2a干扰素刺激MX蛋白合成。提供了这些模型的其他用途列表。这些模型可以很容易地扩展以适应其他复杂性，如非平稳或昼夜基线、平衡延迟、前体池的消耗或积累、S形或其他机制。具有逻辑机制基础的间接反应模型解释了许多反应中的时间延迟，并且在临床药理学中广泛适用。
