Iafrate R P, Yost R L, Curry S H, Gotz V P, Caranasos G J
Pharmacotherapy. 1983 Mar-Apr;3(2 Pt 1):118-24.
Each of ten non-smoking, healthy male volunteers between the ages of 20 and 30 and within 10% of their ideal body weight received four nitroglycerin ointment (NTG-O) treatments: 1/2" NTG-O over 3.94 in2 and 7.88 in2, and 1" NTG-O over 3.94 in2 and 7.88 in2 in a randomized order. Eleven blood samples and 22 determinations of heart rate and blood pressure were obtained over each 6-hour study period. Nitroglycerin plasma concentrations were determined by gas-liquid chromatography with electron capture detection. Area under the nitroglycerin plasma concentration-time curve (AUC), peak plasma concentration (Cmax), and time to peak concentration (Tmax) were determined for each study. Cmax and AUC values were corrected for the actual dose applied. Differences between AUC, Cmax and Tmax were tested using repeated measures analysis of variance. Change in surface area had no statistically significant effect on AUC, Cmax and Tmax. Mean AUC for the 1/2" and 1" doses differed (648 vs 2003 ng.ml-1 min, p = 0.016), as did Cmax (4.6 vs 12.4 ng.ml-1, p = 0.022); however, there was no correlation between individual doses and AUCs. Generally, NTG plasma concentrations within the proposed therapeutic range of 1.2-11.1 ng.ml-1 were detectable throughout each study interval. These data suggest that continuous absorption occurred throughout the 6-hour dosing interval, that a trend toward increased AUC and Cmax occurred with the larger surface area, and that, in general, doubling the dose of NTG-O doubles the AUC.
10名年龄在20至30岁之间、体重在理想体重的10%以内的非吸烟健康男性志愿者，每人接受了4次硝酸甘油软膏（NTG - O）治疗：以随机顺序分别在3.94平方英寸和7.88平方英寸面积上涂抹1/2英寸NTG - O，以及在3.94平方英寸和7.88平方英寸面积上涂抹1英寸NTG - O。在每个6小时的研究期间采集11份血样，并进行22次心率和血压测定。采用电子捕获检测的气液色谱法测定硝酸甘油血浆浓度。为每项研究测定硝酸甘油血浆浓度 - 时间曲线下面积（AUC）、血浆峰浓度（Cmax）和达峰时间（Tmax）。Cmax和AUC值根据实际给药剂量进行校正。使用重复测量方差分析检验AUC、Cmax和Tmax之间的差异。表面积的变化对AUC、Cmax和Tmax没有统计学上的显著影响。1/2英寸和1英寸剂量的平均AUC不同（分别为648与2003 ng·ml⁻¹·min，p = 0.016），Cmax也不同（分别为4.6与12.4 ng·ml⁻¹，p = 0.022）；然而，个体剂量与AUC之间没有相关性。一般来说，在整个研究期间，在1.2 - 11.1 ng·ml⁻¹的建议治疗范围内均可检测到NTG血浆浓度。这些数据表明，在整个6小时给药间隔内持续发生吸收，随着表面积增大，AUC和Cmax有增加的趋势，并且一般来说，NTG - O剂量加倍，AUC也加倍。
