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Determination of enalapril and enalaprilat by enzyme linked immunosorbent assays: application to pharmacokinetic and pharmacodynamic analysis
Author(s) -
Matalka Khalid,
Arafat Tawfiq,
Hamad Mohammad,
Jehanli Ahmed
Publication year - 2002
Publication title -
fundamental and clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.655
H-Index - 73
eISSN - 1472-8206
pISSN - 0767-3981
DOI - 10.1046/j.1472-8206.2002.00087.x
Subject(s) - enalaprilat , enalapril , pharmacokinetics , chemistry , angiotensin converting enzyme , ace inhibitor , enalapril maleate , enzyme inhibitor , endocrinology , pharmacology , medicine , enzyme , blood pressure , biochemistry
We have developed two enzyme linked immunosorbent assay (ELISA) methods for determining enalapril and enalaprilat in plasma. In this study, 48 healthy subjects received an oral dose of either 10 or 20 mg of enalapril and plasma concentrations of enalapril and enalaprilat were determined by their specific ELISA methods. These plasma concentrations and blood pressure measurements were applied to evaluate the pharmacokinetic (PK) and pharmacodynamic (PD) parameters of both enalapril and enalaprilat. The enalapril values for the area under the curve (AUC 0→∞ ) were 480 ± 216 and 832 ± 325 ngh/mL, maximum plasma concentrations (C max ) were 310 ± 187 and 481 ± 185 ng/mL, and times required to reach the maximum concentration (t max ) were 1.13 ± 0.22 and 1.09 ± 0.33 h for 10 and 20 mg doses, respectively. The enalaprilat values for AUC 0→∞ were 256 ± 122 and 383 ± 158 ngh/mL, C max values were 57 ± 29 and 72.9 ± 33.6 ng/mL and t max values were 4.28 ± 1.45 and 4.05 ± 01.22 h for 10 and 20 mg doses, respectively. The C max values of enalapril were ∼10 times higher than those in the literature, which were determined by angiotensin converting enzyme (ACE) inhibition assays following alkaline hydrolysis, but similar to those of enalaprilat. The PD profiles revealed a significant correlation between enalaprilat concentrations in plasma and the decrease in systolic and diastolic blood pressures ( r =−0.95 with P < 0.001 and r =−0.95 with P < 0.001), respectively, following a single oral dose of enalapril. These ELISA methods have the advantage of being simple, accurate, sensitive, and do not depend on enalaprilat binding to ACE. Such methods can be used for analysis and kinetic testing of enalapril and enalaprilat in biological fluids.