Fenichel R R, Lipicky R J
Division of Cardio-Renal Drug Products, United States Food and Drug Administration, Rockville, Maryland 20857, USA.
Am J Hypertens. 1996 Oct;9(10 Pt 2):105S-107S; discussion 108S-109S. doi: 10.1016/0895-7061(96)00272-5.
Blood pressure in hypertensives (treated or untreated) varies over the course of the day, and, although animal models and human intervention studies have demonstrated that the ill effects of hypertension are mediated by the pressure itself, and not by some confounder, it remains unknown what time-related function of pressure (simple mean, root-mean-square, duration of pressure above some threshold, and so on) might be the best predictor of hypertension-related morbidity There is no accepted means of describing the time course of blood pressure, let alone a difference between two such descriptions, which might then be a description of the time course of a drug effect. In a document dated 1988, the US Food and Drug Administration (FDA) defined the trough-to-peak drug-effect ratio and indicated that drug approval would be granted only when values of this statistic were satisfactory. The FDA's belief in the importance of the time-course of drug effect has grown stronger over time, but the idea that only drugs with certain trough-to-peak ratios could be approved was discarded by the FDA within months of its appearance. In recent years, more promising means of assessing the time-course of drug effect have begun to take shape.
高血压患者（无论是否接受治疗）的血压在一天中会有所变化。尽管动物模型和人体干预研究表明，高血压的不良影响是由血压本身介导的，而非某些混杂因素，但目前仍不清楚与时间相关的血压功能（如简单平均值、均方根、高于某个阈值的血压持续时间等）中，哪一种可能是高血压相关发病率的最佳预测指标。目前尚无公认的描述血压时间进程的方法，更不用说两种此类描述之间的差异了，而这种差异可能就是药物效应时间进程的一种描述。在一份日期为1988年的文件中，美国食品药品监督管理局（FDA）定义了谷峰药物效应比，并表示只有当该统计值令人满意时才会批准药物。随着时间的推移，FDA对药物效应时间进程重要性的信念日益增强，但仅批准具有特定谷峰比的药物这一想法在其提出后的几个月内就被FDA摒弃了。近年来，评估药物效应时间进程的更有前景的方法已开始形成。
