Tolerance to isosorbide dinitrate: rate of development and reversal.
Tolerance to isosorbide dinitrate: rate of development and reversal.
复制标题
对硝酸异山梨酯的耐受性：发展速度和逆转。
DOI：
10.1161/01.cir.68.5.1074
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发表时间：
1983
期刊：
影响因子：
37.8
通讯作者：
Stone,JA
中科院分区：
文献类型：
--
作者：
Parker,JO;Fung,HL;Ruggirello,D;Stone,JA
在对照阶段舌下含服 5 mg ISDN、每 6 小时口服 15 mg ISDN 治疗 48 小时后以及随后每天 4 次用安慰剂代替 ISDN 的 48 小时后，测定了 10 名慢性稳定型心绞痛患者的循环反应和血浆浓度。最初，舌下含服 ISDN 可使仰卧位和站立位的收缩压和舒张压大幅降低，但口服 ISDN 治疗 45 小时后，两种体位的血管抑制反应均显着减弱。随后，当用安慰剂替代 ISDN 时，最初看到的循环反应在 21 小时内恢复。口服 ISDN 给药 48 小时后（即耐受状态），测试舌下给药后的血浆 ISDN 浓度略高于研究开始时。这表明耐受性不太可能是由生物利用度降低或 ISDN 加速消除引起的。耐受性可能与 ISDN 代谢物的积累有关。 ISDN 循环反应的减弱可能与 ISDN 持续治疗期间常见的抗心绞痛功效改变有关。
The circulatory response and plasma concentrations of isosorbide dinitrate (ISDN) were determined in 10 patients with chronic, stable angina after administration of 5 mg of sublingual ISDN during the control stage, after 48 hr of therapy with 15 mg of ISDN orally every 6 hr, and subsequently after a 48 hr period when ISDN was substituted by placebo four times daily. Initially, sublingual ISDN induced major reductions in both supine and standing systolic and diastolic blood pressure, but after 45 hr of therapy with oral ISDN, there was a significantly diminished vasodepressor response in both positions. Subsequently, when placebo was substituted for ISDN, the circulatory response initially seen was restored within 21 hr. Plasma ISDN concentrations after the test sublingual dose were slightly higher after 48 hr of oral ISDN dosing (i.e., the tolerant state) than at the start of the study. This suggests that tolerance is unlikely to be caused by reduced bioavailability or accelerated elimination of ISDN. It is possible that tolerance is related to accumulation of ISDN metabolites. The attenuation of the circulatory response to ISDN may be related to the altered antianginal efficacy commonly seen during sustained therapy with ISDN.