Trandolapril. How does it differ from other angiotensin converting enzyme inhibitors?
Among the physicochemical, pharmacokinetic and pharmacodynamic properties that differentiate trandolapril from other angiotensin converting enzyme (ACE) inhibitors, the most clinically relevant ones are those that contribute to the long duration of action of the drug. The long elimination half-life of trandolapril and its strong lipophilicity, high ACE inhibitor potency and high affinity for the ACE cause the drug to have a long biological half-life. The long duration of action of trandolapril may be demonstrated experimentally; near total ACE inhibition is observed 24 hours after single dose administration and there is significant ACE inhibition 72 hours following drug withdrawal after long term therapy. We have analysed the duration of blood pressure lowering during long term therapy with commercially available ACE inhibitors in published studies using ambulatory blood pressure monitoring. On the basis of results from 19 studies undertaken in patients with mild to moderate hypertension, it was possible to reconstruct the curve of the magnitude of blood pressure changes against time. Mean trough: peak ratio calculations showed that once-daily administration produced ratios higher than 50% with enalapril (40 to 80%), lisinopril (40 to 70%) and trandolapril (50 to 100%). Other ACE inhibitors had trough: peak ratios lower than 50%. Despite many methodological limitations, this literature analysis demonstrates that trandolapril has a blood pressure-lowering effect for the full 24-hour period. Studies in which a dose is occasionally omitted show that the blood pressure-lowering effect of trandolapril may last beyond 24 hours.
Zannad
F
F
Department of Clinical Pharmacology, Hôpital Central, University of Nancy I, France.
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D006801:Humans; D006973:Hypertension / Q000188:drug therapy / Q000503:physiopathology; D007211:Indoles / Q000494:pharmacology* / Q000627:therapeutic use
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D007211:Indoles; C052035:trandolapril