The cis- and trans-isomers of enalapril and enalaprilat can be resolved by HPLC and by capillary electrophoresis. The isomeric content of enalapril is perturbed by the ionization of both its carboxyl and amine groups, while the isomeric content of enalaprilat is only perturbed by the ionization of its amine group. Increasing the hydrophobicity of the analyte solvent, as reflected in its molar polarization, increases the Z (cis) content of enalapril and markedly decreases the kinetics for isomerization. Far UV circular dichroic measurements suggest that the increase in Z (cis) content of enalapril is due to protonation of its carboxylate group. Taken together, the in-vitro properties of enalapril and enalaprilat suggest that the in-vivo transformation of the prodrug enalapril to the inhibitor enalaprilat and its delivery to angiotensin-converting enzyme should not be significantly limited by cis/trans-isomerization.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1211/0022357056433 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Toxicological and environmental risks of enalapril and their possible transformation products generated under phototransformation reactions.
Toxicol Rep
December 2024
Universidad Autónoma de Nuevo Léon, UANL, Facultad de Ciencias Químicas, Cd. Universitaria, Av. Universidad s/n, San Nicolas de los Garza, Nuevo Léon 66455, México.
Pharmaceutical active compounds (PACs) in the concentration range of hundreds of ng/L to μg/L have been identified in urban surface water, groundwater, and agricultural land where they cause various health risks. These pollutants are classified as emerging and cannot be efficiently removed by conventional wastewater treatment processes. The use of nano-enabled photocatalysts in the removal of pharmaceuticals in aquatic systems has recently received research attention owing to their enhanced properties and effectiveness.
View Article and Find Full Text PDFHuman enteroid monolayers as a potential alternative for Ussing chamber and Caco-2 monolayers to study passive permeability and drug efflux.
Eur J Pharm Sci
October 2024
Division of Pharmacology and Toxicology, Department of Pharmacy, Radboud University Medical Center, P.O. Box 9101, 6500 HB Nijmegen (Route 137), Nijmegen, the Netherlands; Department of Intensive Care, Radboud University Medical Center, Nijmegen, the Netherlands; Department of Neonatal and Pediatric Intensive Care, Erasmus MC Sophia Children's Hospital, Rotterdam, the Netherlands. Electronic address:
After oral administration, the intestine is the first site of drug absorption, making it a key determinant of the bioavailability of a drug, and hence drug efficacy and safety. Existing non-clinical models of the intestinal barrier in vitro often fail to mimic the barrier and absorption of the human intestine. We explore if human enteroid monolayers are a suitable tool for intestinal absorption studies compared to primary tissue (Ussing chamber) and Caco-2 cells.
View Article and Find Full Text PDFPharmacogenetic study of CES1 gene and enalapril efficacy.
J Appl Genet
September 2024
Rai Medical College Sargodha, Islamabad Road, Sargodha, Pakistan.
Enalapril is an orally administered angiotensin-converting enzyme inhibitor which is widely prescribed to treat hypertension, chronic kidney disease, and heart failure. It is an ester prodrug that needs to be activated by carboxylesterase 1 (CES1). CES1 is a hepatic hydrolase that in vivo biotransforms enalapril to its active form enalaprilat in order to produce its desired pharmacological impact.
View Article and Find Full Text PDFRepurposed drugs in combinations exert additive anti-chikungunya virus activity: an in-vitro study.
Virol J
January 2024
Dengue & Chikungunya Group, ICMR-National Institute of Virology, 20-A, Dr. Ambedkar Road, Pune, Maharashtra, 411001, India.
Chikungunya virus (CHIKV) infection causes chikungunya, a viral disease that currently has no specific antiviral treatment. Several repurposed drug candidates have been investigated for the treatment of the disease. In order to improve the efficacy of the known drugs, combining drugs for treatment is a promising approach.
View Article and Find Full Text PDFA Direct Comparison of Peptide Drug Delivery Systems Based on the Use of Hybrid Calcium Phosphate/Chitosan Nanoparticles versus Unmixed Calcium Phosphate or Chitosan Nanoparticles In Vitro and In Vivo.
Int J Mol Sci
October 2023
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, 117997 Moscow, Russia.
Nanocarriers provide a number of undeniable advantages that could improve the bioavailability of active agents for human, animal, and plant cells. In this study, we compared hybrid nanoparticles (HNPs) consisting of a calcium phosphate core coated with chitosan with unmixed calcium phosphate (CaP) and chitosan nanoparticles (CSNPs) as carriers of a model substrate, enalaprilat. This tripeptide analog is an inhibitor of angiotensin-converting enzyme and was chosen by its ability to lower intraocular pressure (IOP).
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!