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

Article Details

Citation

Zisaki A, Miskovic L, Hatzimanikatis V

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

Curr Pharm Des. 2015;21(6):806-22.

PubMed ID
25341854 [ View in PubMed
]
Abstract

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.

DrugBank Data that Cites this Article

Drugs
Drug Enzymes
DrugEnzymeKindOrganismPharmacological ActionActions
AlprenololCytochrome P450 2D6ProteinHumans
Unknown
Substrate
Details
BetaxololCytochrome P450 2D6ProteinHumans
Unknown
Substrate
Details
BisoprololCytochrome P450 3A4ProteinHumans
Unknown
Substrate
Details
IndapamideCytochrome P450 3A4ProteinHumans
Unknown
Substrate
Details
IndapamideEpoxide hydrolase 1ProteinHumans
Unknown
Substrate
Details
Drug Reactions
Reaction
Details
Details
Details
Drug Interactions
DrugsInteraction
Acebutolol
Thiethylperazine
The serum concentration of Acebutolol can be increased when it is combined with Thiethylperazine.
Acebutolol
Promazine
The serum concentration of Acebutolol can be increased when it is combined with Promazine.
Acebutolol
Prochlorperazine
The serum concentration of Acebutolol can be increased when it is combined with Prochlorperazine.
Acebutolol
Triflupromazine
The serum concentration of Acebutolol can be increased when it is combined with Triflupromazine.
Acebutolol
Fluphenazine
The serum concentration of Acebutolol can be increased when it is combined with Fluphenazine.