Major R M, Taylor T, Chasseaud L F, Darragh A, Lambe R F
Clin Pharmacol Ther. 1984 May;35(5):653-9. doi: 10.1038/clpt.1984.90.
The kinetics of isosorbide 5-mononitrate (5-ISMN) were studied in 12 healthy subjects after intravenous infusion and oral doses of 20 mg. Kinetic parameters calculated by model-independent methods or by assumption of a one-compartment open model were in good agreement. Mean (+/- SD) systemic clearance of 5-ISMN was 127 +/- 21 ml/min, volume of distribution was 48.5 +/- 6.1 l, t 1/2 was 4.4 +/- 0.5 hr, and mean residence time was 6.2 +/- 0.7 hr. At the end of intravenous infusion of 5-ISMN at a rate of 8 mg/hr for 2.5 hr, mean plasma drug concentrations reached 356 +/- 39 ng/ml. Oral doses of 5-ISMN were essentially completely absorbed (93% +/- 13% systemic availability), and mean peak plasma drug concentrations of 388 +/- 70 ng/ml occurred at 0.83 +/- 0.46 hr. Mean absorption t 1/2 was 19 +/- 12 min. Unlike other vasodilator organic nitrates in clinical use, 5-ISMN is notable for its relatively long t 1/2, essentially complete oral absorption, lack of active metabolites, and low intersubject variability in kinetics.
在12名健康受试者中，研究了静脉输注和口服20毫克单硝酸异山梨酯（5-ISMN）后的动力学情况。通过非模型依赖方法或假设为单室开放模型计算得到的动力学参数吻合良好。5-ISMN的平均（±标准差）全身清除率为127±21毫升/分钟，分布容积为48.5±6.1升，半衰期为4.4±0.5小时，平均驻留时间为6.2±0.7小时。以8毫克/小时的速率静脉输注5-ISMN 2.5小时结束时，平均血浆药物浓度达到356±39纳克/毫升。口服5-ISMN基本完全吸收（全身可用性为93%±13%），平均血浆药物峰浓度388±70纳克/毫升出现在0.83±0.46小时。平均吸收半衰期为19±12分钟。与临床使用的其他血管扩张性有机硝酸盐不同，5-ISMN的特点是半衰期相对较长、口服基本完全吸收、缺乏活性代谢物以及个体间动力学变异性低。
