FDA guidelines on trough: peak ratios in the evaluation of antihypertensive agents. United States Food and Drug Administration.

The proposed guidelines for antihypertensive drugs from the United States Food and Drug Administration (FDA) suggest that a trough: peak ratio (placebo corrected) of at least 50% should be a requisite for approval in the United States. It is apparent that many existing antihypertensive agents fail to meet this criterion. In contrast, the newer dihydropyridine calcium antagonist lacidipine has a trough:peak ratio greater than 60% which, combined with its other properties, indicates that it is suitable for once-daily administration in hypertension. There is evidence to suggest that a favorable trough:peak ratio may be beneficial in patients who are not fully compliant with the dosage regimen. In addition, a high ratio is indicative of small pharmacologically induced variability in blood pressure: indeed, lacidipine significantly reduces both systolic and mean blood pressure variability. Because blood pressure variability, independent of absolute pressure, is an important determinant of target-organ damage, there is reason to believe that agents that reduce variability may improve the morbidity associated with hypertension.