Lalka D, Griffith R K, Cronenberger C L
Department of Basic Pharmaceutical Sciences, School of Pharmacy, West Virginia University, Morgantown 26506.
J Clin Pharmacol. 1993 Jul;33(7):657-69. doi: 10.1002/j.1552-4604.1993.tb04720.x.
The first-pass hepatic metabolism of a number of important therapeutic agents is inconsistent with traditional models that assume that the hepatic extraction ratio of a drug is constant in each individual (independent of the concentration of drug in the hepatic sinusoidal blood and also independent of the history of exposure to the drug). In this review, the authors examine the first-pass metabolism of five "problematic drugs" (propranolol, lidocaine, propafenone, verapamil, and nitroglycerin). Each of these compounds has unique facets to its hepatic clearance and pharmacokinetics as well as striking similarities. Selected aspects of first-pass metabolism are reviewed, and a theory that may explain some of the unusual behavior of the four lipophilic bases (propranolol, lidocaine, propafenone, and verapamil) is presented. Finally, the unusual and variable clearance of nitroglycerin is discussed.
许多重要治疗药物的首过肝代谢与传统模型不一致，传统模型假定药物的肝提取率在每个个体中是恒定的（与肝窦状隙血液中的药物浓度无关，也与药物暴露史无关）。在本综述中，作者研究了五种“问题药物”（普萘洛尔、利多卡因、普罗帕酮、维拉帕米和硝酸甘油）的首过代谢。这些化合物中的每一种在其肝清除率和药代动力学方面都有独特的方面，也有显著的相似之处。本文综述了首过代谢的选定方面，并提出了一种理论，该理论可能解释四种亲脂性碱（普萘洛尔、利多卡因、普罗帕酮和维拉帕米）的一些异常行为。最后，讨论了硝酸甘油异常且多变的清除率。
