Oral isosorbide dinitrate in angina pectoris: comparison of duration of action an dose-response relation during acute and sustained therapy.
Oral isosorbide dinitrate in angina pectoris: comparison of duration of action an dose-response relation during acute and sustained therapy.
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口服硝酸异山梨酯治疗心绞痛：急性和持续治疗期间作用持续时间和剂量反应关系的比较。
DOI：
10.1016/0002-9149(82)90518-5
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发表时间：
1982
期刊：
影响因子：
--
通讯作者：
Parker,JO
中科院分区：
文献类型：
--
作者：
Thadani,U;Fung,HL;Darke,AC;Parker,JO
本文报告12例心绞痛患者口服不同剂量硝酸异山梨酯的疗效。硝酸异山梨酯30、60和120 mg持续给药后，平均血药浓度和血药浓度-时间曲线下面积均高于急性给药（P < 0.01）。急性期站立位收缩压下降幅度大于持续治疗期（p < 0.001）。这种收缩压降低与剂量相关，在急性治疗期间持续8小时，但与剂量无关，在持续治疗期间仅持续4小时。与安慰剂治疗相比，每次服用硝酸异山梨酯8小时后，急性治疗期间至心绞痛发作和中度心绞痛发展的运动持续时间显著增加，但持续治疗期间仅增加2小时。在急性治疗期间，单次给予15或30 mg硝酸异山梨酯产生了与60或120 mg剂量相似的运动耐量改善。在持续治疗期间（15 mg，每日4次），运动耐量增加到与30、60或120 mg，每日4次剂量相同的幅度。在大多数患者中，运动耐量的最大改善发生在剂量为15或30 mg每日4次后。结论是，在持续治疗与硝酸异山梨酯，抗心绞痛和循环效应的部分耐受性发展迅速。
The effects of different oral doses of isosorbide dinitrate administered acutely and four times daily during sustained therapy were studied in 12 patients with angina pectoris. After administration of 30, 60 and 120 mg of isosorbide dinitrate, the average plasma concentrations were higher and the area under the plasma concentration time curve was greater during sustained than during acute therapy (p < 0.01). Reduction in standing systolic blood pressure was greater during acute than during sustained therapy (p < 0.001). This reduction in systolic blood pressure was dose-related and persisted for 8 hours during acute therapy, but was not dose-related and was demonstrable for only 4 hours during sustained therapy. Compared with placebo therapy, exercise duration to the onset of angina and to the development of moderate angina increased significantly after each dose of isosorbide dinitrate for 8 hours during acute therapy but for only 2 hours during sustained therapy. During acute therapy, administration of a single dose of 15 or 30 mg of isosorbide dinitrate produced similar improvement in exercise tolerance as did a dose of 60 or 120 mg. During sustained therapy (15 mg four times daily), exercise tolerance increased to the same magnitude as with doses of 30, 60 or 120 mg four times daily. In most patients, near maximal improvement in exercise tolerance occurred after a dose of 15 or 30 mg four times daily.It is concluded that during sustained therapy with isosorbide dinitrate, partial tolerance to the antianginal and circulatory effects develops rapidly.
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DOI：
10.1136/oem.26.2.150
发表时间：
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期刊：
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