Boertz A, Bonn R
Z Kardiol. 1986;75 Suppl 3:57-60.
Previous studies carried out with ISDN prove that long lasting, unfluctuating plasma concentrations--e.g. above 300 ng IS-5-N/ml--cause a severe loss of action. This could be cancelled by administration of isosorbide dinitrate (ISDN) according to a regimen in which an interval with considerably reduced nitrate levels is guaranteed. On the other hand a dosage regimen which leads to steady state plasma concentrations which fluctuate between 100 and 300 ng IS-5-N/ml (after 3 times daily 20 mg ISDN) showed no clinically significant loss of efficacy even after 4 weeks of application. Based on these findings a therapy like once daily 120 mg ISDN sustained release which guarantees plasma levels of up to 600 ng IS-5-N/ml (over the active day of the patient) with an interval of nitrate levels down to 100 ng (overnight) could be judged as efficient. As recent studies showed there is no clinically found loss of efficacy after four week application. With regard to a better compliance this regimen seemed to be the optimum.
先前使用硝酸异山梨酯（ISDN）进行的研究证明，血浆浓度持久且无波动——例如高于300 ng IS-5-N/ml——会导致严重的药效丧失。这可以通过按照保证有相当长一段时间硝酸盐水平显著降低的方案给予硝酸异山梨酯（ISDN）来消除。另一方面，一种导致稳态血浆浓度在100至300 ng IS-5-N/ml之间波动（每日3次，每次20 mg ISDN后）的给药方案，即使在应用4周后也未显示出临床上显著的疗效丧失。基于这些发现，像每日1次120 mg ISDN缓释制剂这样的疗法可被判定为有效，该疗法能保证血浆水平高达600 ng IS-5-N/ml（在患者的活动日内），且硝酸盐水平间隔期降至100 ng（夜间）。正如最近的研究表明，应用4周后临床上未发现疗效丧失。就更好的依从性而言，该方案似乎是最佳的。
