Aren't we suppose to see the peak effect after 4-5 half lives of the drug? After reaching the Css? I did view the drug monograph, and it states that the peak effect is seen after 6 hrs not after 4-5 days with once daily dosing?
The pik effect/concentration of lisinopril that is achieved 6 hours after oral administration, could be explained by its long duration of action (24 hours), and its long half-life (12 hours). Lisinopril has carboxyl group, does not metabolise in liver, does not have active metabolites, does not bind to protein and is eliminated as unchanged by renal excretion. On the other hand, captopril has sylfhydryl group, its pik effect is achieved after 1-2 hours after oral administration, its duration of action is 6-10 hours (dose-related), its half-life is
Dr.Milena, aren't we suppose to see the peak effect after reaching Css instead? i.e after 3 days?
The term "peak effect" that you find in the product information, actually means "peak serum concentration" which enables "peak effect" of the one tablet of lisinopril after oral administration.
So Dr.Milena, the maximum effect is expected to be seen after 3-4 days right?
ACE-inhibitor may have delayed response due to physiological intermediates (not only due to its long half-life). The physiological mediators of the blood pressure fall (due to angiotensin converting enzyme inhibition) are angiotensin (rapid effect) and sodium (slow effect). It can take at least a week to see the full blood pressure lowering effect because of the long half-life of sodium.
Dr.Milena, can you give me references ? Especially the part which states that it takes at least a week?
Please see the presentation of Prof. Nick Holford (slide 21), using the link: http://holford.fmhs.auckland.ac.nz/docs/delayed-and-cumulative-drug-effects.pdf.
Additionally, a number of clinical trials of antihypertensive drugs from many drug classes (incl. ACE inhibitors) have suggested that maximum BP lowering takes 4 to 6 weeks or longer after initiation of drug treatment (Weir MR. Speed and duration of dose titration with angiotensin-converting enzyme inhibitor quinapril: relationship with efficacy in patients with moderate hypertension. J Hum Hypertens. 1994; 8725-8730.).
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