Jusko W J, Ko H C
Department of Pharmaceutics, School of Pharmacy, State University of New York at Buffalo 14260.
Clin Pharmacol Ther. 1994 Oct;56(4):406-19. doi: 10.1038/clpt.1994.155.
A family of four basic physiologic indirect response models has been proposed to account for the pharmacodynamics of drugs that act by way of inhibition or stimulation of the production or loss of endogenous substances or mediators. Such models were applied previously to account for the anticoagulant effects of warfarin, adrenal suppression by corticosteroids, cell trafficking effects of corticosteroids, antipyretic effects of ibuprofen, and aldose reductase inhibition. Additional responses that can be readily characterized with such models include muscular contraction from pyridostigmine, diuresis from furosemide, bronchodilation from terbutaline, prolactin secretion after cimetidine, and potassium suppression by terbutaline. This report shows that indirect response models, rather than "link" or "hypothetical effect compartment" models, may be more appropriate for diverse drugs when time lags exist between plasma or biophase drug concentrations and the time course of pharmacodynamic responses.
已经提出了一个由四个基本生理间接反应模型组成的家族，用于解释通过抑制或刺激内源性物质或介质的产生或损失起作用的药物的药效学。此类模型先前已用于解释华法林的抗凝作用、皮质类固醇对肾上腺的抑制作用、皮质类固醇的细胞转运作用、布洛芬的解热作用以及醛糖还原酶抑制作用。可以用此类模型轻松表征的其他反应包括新斯的明引起的肌肉收缩、呋塞米引起的利尿、特布他林引起的支气管扩张、西咪替丁后催乳素分泌以及特布他林引起的钾抑制。本报告表明，当血浆或生物相药物浓度与药效学反应的时间进程之间存在时间滞后时，间接反应模型而非“链接”或“假设效应室”模型可能更适用于多种药物。
