Enalapril/enalaprilat

Swaan, P. W., Stenhouwer, M. C., Tukker, J., Molecular mechanism for the relative binding affinity to the intestinal peptide carrier. Comparison of three ACE-inhibitors enalapril, enalaprilat, and lisinopril, Biochim. Biophys. Acta 1995, 3236, 31-38. 

P. W. Swaan, M. C. Stehouwer, J. J. Tukker, Molecular Mechanism for the Relative Binding Affinity to the Intestinal Peptide Carrier. Comparison of Three ACE-Inhibitors Enalapril, Enalaprilat and Lisinopril , Biochim. Biophys. Acta 1995, 1236, 31-38. 

Ester hydrolysis does not invariably lead to inactive metabolites, as exemplified by acetylsalicylic acid. The cleavage product, salicylic acid, retains pharmacological activity. In certain cases, drugs are administered in the form of esters in order to facilitate uptake into the body (enalapril-enalaprilat, p.128 testosterone decanoate-testosterone, p. 248) or to reduce irritation of the gastric or Luellmann, Color Atlas of Pharmacology All rights reserved. Usage subject to terms... 

Aliskiren, enalapril, enalaprilat/urine UHPLC MS/MS Column Poroshell 120 EC-C18 (100 X 2.1 mm 2.7 pm) Mobile phase Solvent A 0.1 % HCOOH in water Solvent B ACN (gradient elution) Detection MS/MS, ionization ESI Extraction MEPS/ sorbent C8/elution MeOH LOQ 0.01 ng/mL [70]... 

Figure 8.7. Molecular structure of the ACE-inhib-itors enalapril, enalaprilat, and lisinopril. Enalapril and lisinopril are substrates for PepTl.

Extracted metabolites, quinaprilat Simultaneous enalapril, enalaprilat... 

Enalaprilat and SQ27,519 are angiotensin-converting enzyme (ACE) inhibitors with poor oral absorption. Enalapril and fosinopril are dipeptide and amino acid derivatives of enalaprilat and SQ27,519, respectively [51] (Fig. 10). Both prodrugs are converted via deesterification to the active drug by hepatic biotransformation. In situ rat perfusion of enalapril indicated a nonpassive absorption mechanism via the small peptide carrier-mediated transport system. In contrast to the active parent, enalapril renders enalaprilat more peptide-like, with higher apparent affinity for the peptide carrier. The absorption of fosinopril was predominantly passive. Carrier-mediated transport was not demonstrated, but neither was its existence ruled out. 

Let me emphasize the magnitude of the problem with a simple example. I was once asked to estimate the number of compounds covered by a typical issued patent for a drug of commercial interest. The patent that I selected to analyze was for enalapril, a prominent prodrug ACE inhibitor with a well-established commercial market. Given the parameters as outlined in the patent covering enalapril, an estimation of the total number of compounds included in the generic claim for enalaprilat, the active... 

ACE inhibitors, such as captopril and enalaprilat, the active metabolite of enalapril, occupy the enzyme as false substrates. Affinity significantly influences efficacy and rate of elimination. 

For conversion from IV to oral therapy, the recommended initial dose of enalapril maleate tablets for patients who have responded to 0.625 mg enalaprilat every 6 hours is 2.5 mg once a day with subsequent dosage adjustment as needed. 

The answer is h. (Katzung, pp 172-174.) Enalapril is converted to its active form by de-esterification to enalaprilat, which is capable of inhibiting the ACE, peptidyl peptidase. Levels of bradykinin also increase... 

Angiotensin converting enzyme (ACE) inhibitors benazepril captopril cilazapril enalaprilat enalapril maleate fosinopril sodium lisinopril... 

Enalapril is an oral prodrug that is converted by hydrolysis to a converting enzyme inhibitor, enalaprilat, with effects similar to those of captopril. Enalaprilat itself is available only for intravenous use, primarily for hypertensive emergencies. Lisinopril is a lysine derivative of enalaprilat. Benazepril, fosinopril, moexipril, perindopril, quinapril, ramipril, and trandolapril are other long-acting members of the class. All are prodrugs, like enalapril, and are converted to the active agents by hydrolysis, primarily in the liver. 

Captopril s pharmacokinetic parameters and dosing recommendations are set forth in Table 11-2. Peak concentrations of enalaprilat, the active metabolite of enalapril, occur 3-4 hours after dosing with enalapril. The half-life of enalaprilat is about 11 hours. Typical doses of enalapril are 10-20 mg once or twice daily. Lisinopril has a half-life of 12 hours. Doses of 10-80 mg once daily are effective in most patients. All of the ACE inhibitors except fosinopril and moexipril are eliminated primarily by the kidneys doses of these drugs should be reduced in patients with renal insufficiency. 

Peak concentrations of enalaprilat, the active metabolite, occur 3-4 hours after dosing with enalapril. The half-life of enalaprilat is about 11 hours. Typical doses of enalapril are 10-20 mg once or twice daily. 

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