Reichek N, Priest C, Zimrin D, Chandler T, Sutton M S
Am J Cardiol. 1984 Jul 1;54(1):1-7. doi: 10.1016/0002-9149(84)90295-9.
Nitroglycerin (NTG) patches provide potentially therapeutic NTG blood levels for 24 hours, but their effects on exercise tolerance (ExT) in patients with angina have not been well characterized. Therefore, blinded, randomized trials were performed of the acute effects of both low-dose and maximal-tolerated-dose NTG patches and placebo on ExT in 14 patients with coronary artery disease and typical exertional angina. The bicycle exercise protocol of the National Institutes of Health was used and sublingual NTG administered as a positive control. In 7 subjects, low-dose patches produced no statistically significant effect on ExT at 4, 8 or 24 hours after administration. Comparable doses of sublingual and oral isosorbide dinitrate, NTG ointment and transmucosal NTG in previous studies have produced effects similar to those of conventional doses of sublingual NTG. Maximally tolerated doses of 2 types of NTG patches were then tested. The first (n = 8, mean NTG dose delivered 25 mg) produced increases in ExT of 82 and 72 seconds at 4 and 8 hours, respectively (both p less than 0.01), but was ineffective at 24 hours. The second patch type (n = 5, mean NTG dose delivered 22 mg) was also ineffective at 24 hours. Furthermore, even at maximal doses, peak effects on ExT were about half of those of sublingual NTG. Thus, NTG patches, even at maximal doses, appear to have smaller therapeutic effects than other long-acting nitrates and are ineffective at 24 hours. These results suggest rapid attenuation of NTG effect during prolonged maintenance of constant blood levels.
硝酸甘油(NTG)贴片可使NTG血药浓度维持在潜在治疗水平达24小时,但它们对心绞痛患者运动耐量(ExT)的影响尚未得到充分研究。因此,我们对14例冠状动脉疾病和典型劳力性心绞痛患者进行了一项双盲、随机试验,以研究低剂量和最大耐受剂量的NTG贴片及安慰剂对ExT的急性影响。采用美国国立卫生研究院的自行车运动方案,并给予舌下含服NTG作为阳性对照。在7名受试者中,低剂量贴片在给药后4、8或24小时对ExT均未产生统计学显著影响。在先前的研究中,相当剂量的舌下含服和口服硝酸异山梨酯、NTG软膏及经黏膜NTG产生的效果与传统剂量的舌下含服NTG相似。随后对两种类型的NTG贴片最大耐受剂量进行了测试。第一种(n = 8,平均释放NTG剂量25 mg)在4小时和8小时时分别使ExT增加了82秒和72秒(均p < 0.01),但在24小时时无效。第二种贴片类型(n = 5,平均释放NTG剂量22 mg)在24小时时也无效。此外,即使在最大剂量下,对ExT的峰值效应也仅约为舌下含服NTG的一半。因此,NTG贴片即使在最大剂量下,其治疗效果似乎也比其他长效硝酸盐小,且在24小时时无效。这些结果提示,在持续维持恒定血药浓度期间,NTG的效应会迅速减弱。