Fung H L
Am J Med. 1983 Jun 27;74(6B):13-20. doi: 10.1016/0002-9343(83)90849-5.
The current literature on the human pharmacokinetics of nitroglycerin, isosorbide dinitrate, and isosorbide mononitrates is briefly reviewed and evaluated. The pharmacokinetics of nitroglycerin are unusual in that its systemic clearance is extremely large and that there is a distinct arterial-venous gradient in plasma concentration. These features had created substantial difficulties in the documentation and interpretation of nitroglycerin plasma concentrations and pharmacokinetics. Studies with isosorbide dinitrate showed that this nitrate is absorbed as intact drug at about 20 percent of a comparable intravenous dose, firmly disproving a previous belief that orally administered nitrate is completely degraded by presystemic metabolism. The current data suggest that plasma nitrate concentration may relate to some of its pharmacologic effects after short-term dosing, but the concentration-response relationship is complex after long-term dosing. Studies of nitrate pharmacokinetics in their presumed sites of action, namely, the vasculature, appear to be useful for the further understanding of the mechanism of action for these vasodilators.
本文简要回顾并评估了目前关于硝酸甘油、异山梨醇二硝酸酯和异山梨醇单硝酸酯人体药代动力学的文献。硝酸甘油的药代动力学不同寻常，其全身清除率极高，且血浆浓度存在明显的动静脉梯度。这些特性给硝酸甘油血浆浓度和药代动力学的记录与解释带来了很大困难。异山梨醇二硝酸酯的研究表明，该硝酸盐以完整药物形式被吸收，约为静脉注射剂量的20%，这有力地反驳了之前认为口服硝酸盐会被首过代谢完全降解的观点。目前的数据表明，短期给药后血浆硝酸盐浓度可能与其某些药理作用有关，但长期给药后浓度-反应关系较为复杂。在假定的作用部位即脉管系统中研究硝酸盐药代动力学，似乎有助于进一步了解这些血管扩张剂的作用机制。
