Beermann B
Acta Pharmacol Toxicol (Copenh). 1986;59 Suppl 6:35-9.
There is strong evidence that nitrate tolerance develops rapidly during repeated administration in the systemic resistance vascular bed and that there exists cross tolerance between different nitrates. There are divergent opinions on how tolerance in the systemic capacitance and the pulmonary vascular bed develops. This may be explained by real differences in tolerance development in ischemic heart disease and congestive heart failure but also by the use of several different preparations of nitrates in the studies performed. Available data on the pharmacokinetics of nitrates present a complex picture with highly variable bioavailability, clearance and apparent volume of distribution both inter- and intraindividually. It is suggested that nitrate tolerance should be studied in very homogeneous groups of patients with well defined hemodynamics. The nitrate used should have a very short half-life allowing for simulation of various modes of administration by intravenous infusion.
有强有力的证据表明，在全身阻力血管床反复给药期间，硝酸盐耐受性会迅速发展，并且不同硝酸盐之间存在交叉耐受性。关于全身容量血管和肺血管床的耐受性如何发展，存在不同观点。这可能是由于缺血性心脏病和充血性心力衰竭中耐受性发展的实际差异，也可能是由于在进行的研究中使用了几种不同的硝酸盐制剂。现有的硝酸盐药代动力学数据呈现出一幅复杂的图景，个体间和个体内的生物利用度、清除率和表观分布容积变化很大。建议在血流动力学明确的非常同质的患者群体中研究硝酸盐耐受性。所使用的硝酸盐应具有非常短的半衰期，以便通过静脉输注模拟各种给药方式。
