title: FDA guidelines on trough: peak ratios in the evaluation of antihypertensive agents. United States Food and Drug Administration.
abstract: 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.
authors.affiliation: University Department of Medicine and Therapeutics, Gardiner Institute, Western Infirmary, Glasgow, Scotland.
authors.forename: P A
authors.initials: PA
authors.lastname: Meredith
authors.forename: H L
authors.initials: HL
authors.lastname: Elliott
mesh_terms: D000959:Antihypertensive Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects; D002940:Circadian Rhythm / Q000502:physiology; D004341:Drug Evaluation; D006801:Humans; D006973:Hypertension / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D014481:United States; D014486:United States Food and Drug Administration
chemical_list: D000959:Antihypertensive Agents