Zannad F
University of Nancy, Hôpital Central, France.
Am J Hypertens. 1995 Oct;8(10 Pt 2):75S-81S. doi: 10.1016/0895-7061(95)00194-8.
Duration of action of an angiotensin converting enzyme (ACE) inhibitor is not solely related to its individual elimination half-life. It is also determined by its ACE inhibiting potency and affinity for ACE. Its degree of lipophilicity is also an important factor in determining tissue penetration. Any attempt to calculate the duration of action, and, consequently, the interdosing interval, of an ACE inhibitor should take into account and integrate all these variables. The measurement (or the calculation) of each of these variables is not in itself an easy task and is very much prone to error. Given the failure of pharmacokinetic and pharmacodynamic studies to provide an adequate and simple method capable of predicting reliably the time-effect relationship of ACE inhibitors, it is obvious that the pragmatic way to determine this time-effect profile is to monitor blood pressure changes during the clinical use of a given ACE inhibitor. Because very little information is available for many ACE inhibitors concerning their trough/peak ratio, we have recently reviewed all the published studies assessing the antihypertensive efficacy of commercially available ACE inhibitors with ambulatory blood pressure monitoring. Our literature analysis suggests that not all once daily ACE inhibitors comply with the Food and Drug Administration requirement of a trough/peak ratio higher than 50%. However, current evidence suggests that the definition of this ratio is dependent upon the methodology employed for its determination. The only validated analytical approach that is based on blood pressure measurements in a few confined patients, during phase II dose-finding studies. Fuller information may be sought with alternative evaluative approaches based on ambulatory BP measurements in large numbers of patients and in more pragmatic daily life conditions. Although this remains to be demonstrated, long acting ACE inhibitors may provide additional benefits over the shorter acting ones by producing an optimal 24 h and longer therapeutic coverage, with fewer peak-effect related side effects and better control of blood pressure during critical nighttime and early morning hours.
血管紧张素转换酶（ACE）抑制剂的作用持续时间并非仅与其个体消除半衰期相关。它还取决于其对ACE的抑制效力和亲和力。其亲脂性程度也是决定组织穿透力的重要因素。任何计算ACE抑制剂作用持续时间以及给药间隔的尝试都应考虑并整合所有这些变量。对这些变量中的每一个进行测量（或计算）本身并非易事，而且极易出错。鉴于药代动力学和药效学研究未能提供一种足够简单且能可靠预测ACE抑制剂时间-效应关系的方法，显然确定这种时间-效应曲线的实用方法是在临床使用特定ACE抑制剂期间监测血压变化。由于许多ACE抑制剂关于其谷值/峰值比的信息非常少，我们最近回顾了所有已发表的研究，这些研究通过动态血压监测评估了市售ACE抑制剂的降压疗效。我们的文献分析表明，并非所有每日一次的ACE抑制剂都符合美国食品药品监督管理局要求的谷值/峰值比高于50%。然而，目前的证据表明，该比值的定义取决于用于确定它的方法。唯一经过验证的分析方法是在II期剂量探索研究期间，基于少数受限患者的血压测量。通过基于大量患者在更实际的日常生活条件下进行动态血压测量的替代评估方法，可能会获得更全面的信息。尽管这仍有待证明，但长效ACE抑制剂可能比短效ACE抑制剂提供更多益处，因为它能提供最佳的24小时及更长时间的治疗覆盖，与峰值效应相关的副作用更少，并且在关键的夜间和清晨时段能更好地控制血压。
