ANTIHYPERTENSIVES FAIL TROUGH-PEAK CRITERIA

A large range of antihypertensive agents are failing to meet the US Food and Drug Administration's tentative trough-to-peak criteria of 50%, and need to be given more frequently or in different formulations. ACE inhibitors in particular should change from their once-a-day frequency to at least twice a day, according to researchers speaking at the Bayer-sponsored 2nd International Nifedipine Gastrointestinal Therapeutic System (GITS) Symposium in Paris, France.

Peter Meredith, senior lecturer in the department of medicine and therapeutics at the University of Glasgow, Scotland, has performed studies in groups of 10-13 patients. Dr Meredith and his co-worker, Henry Elliott of Western Infirmary in Glasgow, believe that most ACE inhibitors need to be given twice-daily for smooth control of hypertension over 24 hours because of their pharmacokinetic profiles. However, strong commercial pressures to provide convenient once-daily formulations have meant that most of these drugs are given once a day.

The trough-to-peak ratio is the blood pressure decrease at the end of the dosage interval divided by the largest blood pressure decrease during the dosage interval (Dr Meredith corrected all pressures in his study to account for placebo effects). A low trough-to-peak ratio means a greater variation between maximal and minimal blood pressure lowering effect during the dosage interval, so a high trough-to-peak ratio is believed to protect the patient more efficiently against end organ damage. The FDA's draft guidelines for the clinical evaluation of antihypertensive drugs recommend at least a 50% trough-to-peak ratio, because of concerns over cerebral hypotension at peak concentrations in drugs whose dosage has been boosted so that it can be given once a day.