Abstract :
Duration of action of an angiotensin converting enzyme (ACE) inhibitor is not solely related to its individual elimination half-life. It is also determined by its ACE inhibiting potency and affinity for ACE. Its degree of lipophilicity is also an important factor in determining tissue penetration. Any attempt to calculate the duration of action, and, consequently, the interdosing interval, of an ACE inhibitor should take into account and integrate all these variables. The measurement (or the calculation) of each of these variables is not in itself an easy task and is very much prone to error. Given the failure of pharmacokinetic and pharmacodynamic studies to provide an adequate and simple method capable of predicting reliably the time-effect relationship of ACE inhibitors, it is obvious that the pragmatic way to determine this time-effect profile is to monitor blood pressure changes during the clinical use of a given ACE inhibitor. Because very little information is available for many ACE inhibitors concerning their trough/peak ratio, we have recently reviewed all the published studies assessing the antihypertensive efficacy of commercially available ACE inhibitors with ambulatory blood pressure monitoring. Our literature analysis suggests that not all once daily ACE inhibitors comply with the Food and Drug Administration requirement of a trough/peak ratio higher than 50%. However, current evidence suggests that the definition of this ratio is dependent upon the methodology employed for its determination. The only validated analytical approach that is based on blood pressure measurements in a few confined patients, during phase II dose-finding studies. Fuller information may be sought with alternative evaluative approaches based on ambulatory BP measurements in large numbers of patients and in more pragmatic daily life conditions. Although this remains to be demonstrated, long acting ACE inhibitors may provide additional benefits over the shorter acting ones by producing an optimal 24 h and longer therapeutic coverage, with fewer peak-effect related side effects and better control of blood pressure during critical nighttime and early morning hours.
