Miyazaki S, Nonogi H, Goto Y, Sumiyoshi T, Haze K, Hiramori K
Division of Cardiology, National Cardiovascular Center, Suita.
Intern Med. 1995 Sep;34(9):856-62. doi: 10.2169/internalmedicine.34.856.
Therapeutic efficacy of intermittent and continuous injection of isosorbide dinitrate (ISDN) was compared in 22 patients (mean age 64 +/- 10, 18 males and 4 females) with unstable angina at rest. They were randomized into 2 groups that received either continuous (10 mg/h, group A) or intermittent (10 mg/10 min every 2 hours, group B) injection of ISDN for 3 days (phase 1). Each injection protocol was switched (phase 2) and subsequently switched back to the initial protocol (phase 3) in a cross-over fashion. The serum concentrations of ISDN, 2-isosorbide mononitrate (2-ISMN) and 5-ISMN were measured serially during both intermittent and continuous injection protocols. In addition, the incidence and duration of angina and changes in systolic blood pressure were analyzed. There were 3 treatment-failure cases during the intermittent injection period and 1 during the continuous injection period. Three of these treatment-failure cases developed small acute myocardial infarcts despite emergent coronary arteriography followed by intra-coronary thrombolysis and percutaneous balloon angioplasty. There was no difference in therapeutic efficacy between continuous and intermittent ISDN in terms of the incidence, duration of angina attacks and the number of patients whose angina was suppressed. After bolus injection of ISDN (10 mg/10 min), the serum concentration of ISDN increased rapidly and returned to the control level at 60 minutes after the injection. The serum 5-ISMN and 2-ISMN concentrations also increased immediately after injection and then decreased gradually reaching statistically insignificant level to the control values at 60 minutes after injection. With continuous injection, ISDN and its metabolites increased gradually and reached similar but slightly lower serum concentrations to the peak levels during intermittent injection. We conclude that the therapeutic efficacy of intermittent and continuous injection of ISDN is similar in patients with unstable angina.
对22例静息性不稳定型心绞痛患者（平均年龄64±10岁，男18例，女4例）比较了间断和持续注射硝酸异山梨酯（ISDN）的治疗效果。他们被随机分为2组，分别接受持续（10mg/h，A组）或间断（每2小时10mg/10分钟，B组）注射ISDN 3天（第1阶段）。每种注射方案进行切换（第2阶段），随后以交叉方式再切换回初始方案（第3阶段）。在间断和持续注射方案期间连续测定ISDN、2-单硝酸异山梨酯（2-ISMN）和5-ISMN的血清浓度。此外，分析心绞痛的发生率和持续时间以及收缩压的变化。间断注射期间有3例治疗失败病例，持续注射期间有1例。这些治疗失败病例中有3例尽管紧急进行了冠状动脉造影，随后进行了冠状动脉内溶栓和经皮球囊血管成形术，但仍发生了小面积急性心肌梗死。就心绞痛发作的发生率、持续时间以及心绞痛得到抑制的患者数量而言，持续和间断注射ISDN的治疗效果没有差异。静脉推注ISDN（10mg/10分钟）后，ISDN的血清浓度迅速升高，并在注射后60分钟恢复到对照水平。注射后血清5-ISMN和2-ISMN浓度也立即升高，然后逐渐下降，在注射后60分钟降至与对照值无统计学差异的水平。持续注射时，ISDN及其代谢产物逐渐升高，达到与间断注射时峰值水平相似但略低的血清浓度。我们得出结论，对于不稳定型心绞痛患者，间断和持续注射ISDN的治疗效果相似。
