Toyosaki N, Toyo-oka T, Natsume T, Katsuki T, Tateishi T, Yaginuma T, Hosoda S
Department of Cardiology, Jichi Medical School, Tochigi, Japan.
Circulation. 1988 Jun;77(6):1370-5. doi: 10.1161/01.cir.77.6.1370.
The antianginal effects of diltiazem and nifedipine alone and in combination were evaluated in a double-blind, randomized, placebo-controlled trial in 11 patients (nine men and two women, 57 +/- 8 years old) with stable effort angina. Each patient received placebo, 30 mg of diltiazem, 10 mg of nifedipine, and 30 mg of diltiazem plus 10 mg of nifedipine four times daily for 1 week each. Antianginal efficacy was assessed by means of a treadmill exercise test. The exercise tolerance time was significantly prolonged from 235.1 +/- 52 (placebo period) to 342.2 +/- 101 sec by diltiazem (p less than .01) and to 325.6 +/- 73 sec by nifedipine (p less than .01). The drug combination further prolonged exercise time to 451.1 +/- 103 sec, which was significantly longer than the interval attained with either diltiazem (p less than .01) or nifedipine (p less than .01) alone. The plasma concentration of diltiazem was unaffected by the addition of nifedipine, whereas the plasma nifedipine concentration was significantly increased from 34.8 +/- 11 to 106.4 +/- 37 ng/ml (p less than .001) by the concomitant administration of diltiazem. These data suggest that exercise tolerance in patients with effort angina is increased by the concomitant administration of diltiazem and nifedipine associated with an increase in the nifedipine plasma concentration.
在一项针对11例(9例男性和2例女性,年龄57±8岁)稳定型劳力性心绞痛患者的双盲、随机、安慰剂对照试验中,评估了地尔硫䓬和硝苯地平单独及联合使用的抗心绞痛作用。每位患者每天接受4次安慰剂、30毫克地尔硫䓬、10毫克硝苯地平以及30毫克地尔硫䓬加10毫克硝苯地平治疗,每种治疗各持续1周。通过跑步机运动试验评估抗心绞痛疗效。运动耐受时间从安慰剂期的235.1±52秒显著延长至地尔硫䓬治疗后的342.2±101秒(p<0.01),以及硝苯地平治疗后的325.6±73秒(p<0.01)。联合用药进一步将运动时间延长至451.1±103秒,显著长于单独使用地尔硫䓬(p<0.01)或硝苯地平(p<0.01)时达到的时间间隔。地尔硫䓬的血浆浓度不受硝苯地平添加的影响,而同时给予地尔硫䓬时,硝苯地平的血浆浓度从34.8±11显著升高至106.4±37纳克/毫升(p<0.001)。这些数据表明,同时给予地尔硫䓬和硝苯地平可增加劳力性心绞痛患者的运动耐受性,且与硝苯地平血浆浓度升高有关。