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research article

Antihypertensive drugs metabolism: an update to pharmacokinetic profiles and computational approaches

Zisaki, Aikaterini  
•
Miskovic, Ljubisa  
•
Hatzimanikatis, Vassily  
2015
Current Pharmaceutical Design

Drug discovery and development is a high-risk enterprise that requires significant investments in capital, time and scientific expertise. The studies of xenobiotic metabolism remain as one of the main topics in the research and development of drugs, cosmetics and nutritional supplements. Antihypertensive drugs are used for the treatment of high blood pressure, which is one the most frequent symptoms of the patients that undergo cardiovascular diseases such as myocardial infraction and strokes. In current cardiovascular disease pharmacology, four drug clusters - Angiotensin Converting Enzyme Inhibitors, Beta-Blockers, Calcium Channel Blockers and Diuretics - cover the major therapeutic characteristics of the most antihypertensive drugs. The pharmacokinetic and specifically the metabolic profile of the antihypertensive agents are intensively studied because of the broad inter-individual variability on plasma concentrations and the diversity on the efficacy response especially due to the P450 dependent metabolic status they present. Several computational methods have been developed with the aim to: (i) model and better understand the human drug metabolism; and (ii) enhance the experimental investigation of the metabolism of small xenobiotic molecules. The main predictive tools these methods employ are rule-based approaches, quantitative structure metabolism/activity relationships and docking approaches. This review paper provides detailed metabolic profiles of the major clusters of antihypertensive agents, including their metabolites and their metabolizing enzymes, and it also provides specific information concerning the computational approaches that have been used to predict the metabolic profile of several antihypertensive drugs.

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Type
research article
Web of Science ID

WOS:000349459600012

Author(s)
Zisaki, Aikaterini  
Miskovic, Ljubisa  
Hatzimanikatis, Vassily  
Date Issued

2015

Publisher

Bentham Science Publishers

Published in
Current Pharmaceutical Design
Volume

21

Issue

6

Start page

806

End page

822

Subjects

metabolism

•

antihypertensive drugs

•

computational approaches

Editorial or Peer reviewed

REVIEWED

Written at

EPFL

EPFL units
LCSB  
Available on Infoscience
April 2, 2015
Use this identifier to reference this record
https://infoscience.epfl.ch/handle/20.500.14299/112876
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