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Duration of effect is dose-related; at recommended doses, antihypertensive and haemodynamic effects have been shown to be maintained for at least 24 hours. [21] [22] Enalapril has a slower onset of action than Captopril but a greater duration of action. However, unlike Captopril, Enalapril does not have a thiol moiety.
Enalaprilat is the active metabolite of enalapril. It is the first dicarboxylate-containing ACE inhibitor and was developed partly to overcome these limitations of captopril . The thiol functional group of captopril was replaced with a carboxylic acid group, but additional modifications were required to achieve a potency similar to captopril.
Lisinopril is the lysine-analog of enalaprilat, the active metabolite of enalapril. [15] Unlike other ACE inhibitors, it is not a prodrug , is not metabolized by the liver, and is excreted unchanged in the urine.
An equianalgesic chart is a conversion chart that lists equivalent doses of analgesics (drugs used to relieve pain). Equianalgesic charts are used for calculation of an equivalent dose (a dose which would offer an equal amount of analgesia) between different analgesics. [1]
where De is the effective dose, B bioavailability and Da the administered dose. Therefore, if a drug has a bioavailability of 0.8 (or 80%) and it is administered in a dose of 100 mg, the equation will demonstrate the following: De = 0.8 × 100 mg = 80 mg
The main goal of a dose-ranging study is to estimate the response vs. dose given, so as to analyze the efficacy and safety of the drug. Although such a response will nevertheless be available from phase III or phase IV trials, it is important to carry out dose-ranging studies in the earlier phase I or phase II stages.
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The results were 2 active inhibitors: Enalaprilat and Lisinopril. These compounds both have phenylalanine in R position which occupies the S 1 groove in the enzyme. The result was thus these two new, potent tripeptide analogues with zinc-coordinating carboxyl group: Enalaprilat and Lisinopril. [1] [9]