Pharmacokinetics and pharmacodynamics profiles of enalapril maleate in healthy volunteers following determination of enalapril and enalaprilat by two specific enzyme immunoassays.
OBJECTIVE
Most of the pharmacokinetic (PK) parameters for enalapril and enalaprilat were established following determination of the drug and its metabolite, using angiotensin converting enzyme (ACE) inhibition assays. In these methods, enalapril has to be hydrolysed to enalaprilat first and then assayed. The purpose of this study was to re-estimate the PK parameters of enalapril and enalaprilat in healthy volunteers using two specific enzyme immunoassays for enalapril and enalaprilat.


METHODS
The rate and extent of absorption of enalapril and enalaprilat from a 10-mg dose of two enalapril maleate commercial brands (Renetic and Enalapril) were estimated using a two-way-cross over design with 1-week washout period. Blood pressure was also measured at specified time intervals and correlated to enalaprilat plasma concentrations.


RESULTS
For enalapril, the AUC(o-->infinity) values (Mean+/-SD) were 450.0+/-199.5 and 479.6+/-215.6 ng h/mL, Cmax values were 313.5+/-139.6 and 310.1+/-186.6 ng/mL, Tmax values were 1.06+/-0.30 h and 1.13+/-0.22 h, and t1/2 ranged between 0.3 to 6.1 h (1.6+/-1.5) and 0.40 to 5.05 h (1.3+/-1.0), for the two brands. For enalaprilat, the AUC(o-->infinity) values were 266.9+/-122.7 and 255.9+/-121.8 ng h/ml, Cmax values were 54.8+/-29.5 and 57.2+/-29.0 ng/mL, Tmax values were 4.6+/-1.6 h and 4.3+/-1.45 h, and t1/2 ranged between 1.1 to 10.5 h (4.5+/-2.9) and 0.6 to 9.4 h (3.5+/-2.5) for the two brands.


CONCLUSIONS
Cmax values for enalapril are about 10 times those published in the literature and the rate and extent of absorption of the two brands of enalapril and their deesterification to enalaprilat following the administration of either brand were bioequivalent. Secondly, enalaprilat concentrations at 12-24 h following a single oral dose of enalapril in healthy volunteers were lower than those reported in the literature. The values reported here correlated with the return of blood pressure to predose level. Thirdly, enzyme immunoassays for enalapril and enalaprilat are better than ACE inhibition assays and can be used in bioequivalence assessment of enalapril and enalaprilat and for therapeutic drug monitoring in a clinical laboratory setting.
Faculty of Pharmacy and Medical Technology, University of Petra, Amman, Jordan. tarafat@uop.edu.jo
T
T
Arafat
R
R
Awad
M
M
Hamad
R
R
Azzam
A
A
Al-Nasan
A
A
Jehanli
K
K
Matalka
D000042:Absorption; D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology*; D019540:Area Under Curve; D001794:Blood Pressure / Q000187:drug effects; D004656:Enalapril / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology*; D015773:Enalaprilat / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008297:Male; D013810:Therapeutic Equivalency
D000959:Antihypertensive Agents; D004656:Enalapril; D015773:Enalaprilat