Matalka Khalid, Arafat Tawfiq, Hamad Mohammad, Jehanli Ahmed
Faculty of Pharmacy and Medical Technology, The University of Petra, P.O. Box 961343, Amman, Jordan.
Fundam Clin Pharmacol. 2002 Jun;16(3):237-44. doi: 10.1046/j.1472-8206.2002.00087.x.
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)--> infinity ) 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)--> infinity 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 approximately 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.
我们开发了两种酶联免疫吸附测定（ELISA）方法来测定血浆中的依那普利和依那普利拉。在本研究中，48名健康受试者口服10或20mg依那普利，并用其特定的ELISA方法测定血浆中依那普利和依那普利拉的浓度。将这些血浆浓度和血压测量值用于评估依那普利和依那普利拉的药代动力学（PK）和药效学（PD）参数。10mg和20mg剂量的依那普利曲线下面积（AUC(0)→∞）值分别为480±216和832±325ngh/mL，血浆最大浓度（C(max)）分别为310±187和481±185ng/mL，达到最大浓度所需时间（t(max)）分别为1.13±0.22和1.09±0.33小时。10mg和20mg剂量的依那普利拉AUC(0)→∞值分别为256±122和383±158ngh/mL，C(max)值分别为57±29和72.9±33.6ng/mL，t(max)值分别为4.28±1.45和4.05±1.22小时。依那普利的C(max)值比文献中通过碱性水解后血管紧张素转换酶（ACE）抑制试验测定的值高约10倍，但与依那普利拉的C(max)值相似。药效学曲线显示，单次口服依那普利后，血浆中依那普利拉浓度与收缩压和舒张压降低之间存在显著相关性（r = -0.95，P < 0.001；r = -0.95，P < 0.001）。这些ELISA方法具有简单、准确、灵敏的优点，且不依赖于依那普利拉与ACE结合。此类方法可用于生物体液中依那普利和依那普利拉的分析和动力学测试。
