Laufen H, Aumann M, Leitold M
Arzneimittelforschung. 1983;33(7):980-4.
The plasma concentrations of isosorbide dinitrate (ISDN) and its two pharmacologically active metabolites isosorbide 2-mononitrate (IS-2-MN) and isosorbide 5-mononitrate (IS-5-MN) were determined after oral administration of 20 mg ISDN and 20 mg of each of the mononitrates. The mean concentration-time curve of ISDN showed a peak of 51.6 ng/ml 15 min after drug intake, and declined bi-exponentially with a terminal half-life of 36.5 min. The mean concentrations of the simultaneously measured metabolic products IS-2-MN and IS-5-MN reached a maximum of 40.5 ng/ml and 144.4 ng/ml, respectively. In contrast, after the direct ingestion of isosorbide mononitrates, peaks of 409.1 ng/ml (IS-2-MN) and 483.2 ng/ml (IS-5-MN) were observed in the corresponding mean curves. Mean half-lives of 1.72 h for IS-2-MN and 4.20 h for IS-5-MN were calculated. The mean apparent volumes of distribution were 44.5 l (IS-2-MN) and 34.4 l (IS-5-MN), suggesting that the isosorbide mononitrates are distributed throughout the whole body fluid. After ISDN administration, it was estimated that 3.0 mg IS-2-MN and 7.8 mg IS-5-MN reached the systemic circulation. This corresponds to 63% of the ISDN dose being converted to isosorbide mononitrates by metabolic processes.
口服20毫克硝酸异山梨酯（ISDN）以及20毫克每种单硝酸酯后，测定了血浆中硝酸异山梨酯（ISDN）及其两种药理活性代谢物2-单硝酸异山梨酯（IS-2-MN）和5-单硝酸异山梨酯（IS-5-MN）的浓度。ISDN的平均浓度-时间曲线显示，服药后15分钟出现峰值51.6纳克/毫升，并呈双指数下降，终末半衰期为36.5分钟。同时测定的代谢产物IS-2-MN和IS-5-MN的平均浓度分别达到最大值40.5纳克/毫升和144.4纳克/毫升。相比之下，直接摄入单硝酸异山梨酯后，相应的平均曲线中观察到IS-2-MN的峰值为409.1纳克/毫升，IS-5-MN的峰值为483.2纳克/毫升。计算得出IS-2-MN的平均半衰期为1.72小时，IS-5-MN的平均半衰期为4.20小时。IS-2-MN的平均表观分布容积为44.5升，IS-5-MN的平均表观分布容积为34.4升，这表明单硝酸异山梨酯分布于全身体液中。服用ISDN后，估计有3.0毫克IS-2-MN和7.8毫克IS-5-MN进入体循环。这相当于ISDN剂量的63%通过代谢过程转化为单硝酸异山梨酯。
