Relationship of serum ACE inhibition to oral dose of enalapril in normotensive volunteers.
OBJECTIVE
To determine the relationship between oral dose of enalapril and parameters describing serum angiotensin converting enzyme (ACE) inhibition.


METHODS
Four different oral doses of enalapril maleate (2.5, 5, 10 and 20 mg) were administered to six healthy normotensive volunteers, in a four-period crossover study. Serum ACE inhibition profiles were determined in each case using a synthetic substrate, hippuryl-histidyl-leucine (HHL). Pharmacodynamic parameters of the drug (Emax and AUEC0-->24) were calculated and their relationship to oral doses investigated using linear regression analysis.


RESULTS
There was no significant relationship between drug dose and the two pharmacodynamic parameters (Emax and AUEC0-->24). The r2 values were 0.548 (F=3.63, P=0.153) and 0.6360 (F=5.24, P=0.106) for Emax and AUEC0-->24, respectively.


CONCLUSIONS
The extent of serum ACE inhibition, as the main determinant of the blood pressure lowering effect of enalapril, is not dose-dependent within the single dose range of 2.5-20 mg.
Rouini
M
M
Biopharmaceutics Division, Department of Pharmaceutics, School of Pharmacy, Tehran University of Medical Sciences, Tehran 14, Iran.
Hamidi
M
M
Ghayoumi
A
A
Ismailpour
A
A
D000284:Administration, Oral; D000328:Adult; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004656:Enalapril / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006801:Humans; D006973:Hypertension / Q000188:drug therapy; D008297:Male; D007703:Peptidyl-Dipeptidase A / Q000032:analysis*
D000806:Angiotensin-Converting Enzyme Inhibitors; D004656:Enalapril; D007703:Peptidyl-Dipeptidase A