Trough/peak ratios of once daily angiotensin converting enzyme inhibitors and calcium antagonists

Abstract

Medications given once daily may increase compliance for treatment of hypertension, if the drugs have a prolonged duration of action. The time-effect profiles for antihypertensive drugs may not depend entirely on pharmacokinetic measurements (plasma levels). Thus, trough/peak effects on blood pressure should be measured. It has been suggested that trough/peak ratios be greater than 50% for optimal 24-h control of pressure. Because very little information is available for many angiotensin converting enzyme (ACE) inhibitors and calcium antagonists concerning their trough/peak ratios and awaiting prospective comparative trials with adequate methodology, we have analyzed the duration of action of blood pressure lowering during long-term therapy with commercially available ACE inhibitors and calcium antagonists in published studies that used ambulatory blood pressure monitoring. Published studies were searched in scientific databases using relevant key words. Twenty-four ACE inhibitor and 34 calcium antagonist studies with comparable methodologies were selected. The mean trough/ peak ratios were computed after reconstruction of the curve of the magnitude of blood pressure changes against time. The results showed that once daily administration of ACE inhibitors produced on average ratios higher than 50% with fosinopril (64%), ramipril (50% to 63%), and trandolapril (50% to 100%). Other studied ACE inhibitors produced ratios on average equal to [enalapril (40% to 64%), cilazapril (10% to 80%), lisinopril (30% to 70%)] or significantly lower than 50% [captopril (25%), benazepril (40%), perindopril (35%), quinapril (10% to 40%), and moexipril (0% to 9%)]. As for once daily calcium antagonists, amlodipine (50% to 100%), lacidipine (40% to 100%), nifedipine Coat-Core (50% to 69%), nifedipine gastrointestinal therapeutic system (GITS) (60% to 94%), as well as various "slow release" formulations of diltiazem (20% to 80%) and verapamil (45% to 100%) had on average ratios higher than 50% whereas felodipine ER (30% to 45%), various slow release formulations of isradipine (10% to 80%), and nitrendipine (10% to 80%) had ratios lower than 50%. Although this retrospective literature analysis may have some theoretical limitations, it suggests that not all once daily ACE inhibitors and calcium antagonists cause trough/peak ratio superior to 50%. This may have important clinical implications.