SLCO1B1 and ABCG2 genotype‐informed phenotypes are related to variation in ramipril exposure

Ramipril is an angiotensin‐converting enzyme inhibitor used for hypertension and heart failure management. To date, scarce literature is available on pharmacogenetic associations affecting ramipril. The goal of this study was to investigate the effect of 120 genetic variants in 34 pharmacogenes (i.e...

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Published in:Basic & clinical pharmacology & toxicology 2024-09, Vol.135 (3), p.295-307
Main Authors: Abbes, Houwaida, Zubiaur, Pablo, Soria‐Chacartegui, Paula, Torre, Tamara, Villapalos‐García, Gonzalo, Candau, Carmen, Rodríguez‐Lopez, Andrea, González‐Iglesias, Eva, Aldama, Marina, Navares‐Gomez, Marcos, Omezzine, Asma, Ochoa, Dolores, Abad‐Santos, Francisco
Format: Article
Language:English
Subjects:
ABCG2
Angiotensin
Congestive heart failure
Enzyme inhibitors
Genetic analysis
Genetic diversity
Genetic variance
Genotype & phenotype
Genotypes
Hypertension
Multivariate analysis
pharmacogenetics
Pharmacokinetics
Phenotypes
Phenotypic variations
ramipril
SLCO1B1
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Summary:Ramipril is an angiotensin‐converting enzyme inhibitor used for hypertension and heart failure management. To date, scarce literature is available on pharmacogenetic associations affecting ramipril. The goal of this study was to investigate the effect of 120 genetic variants in 34 pharmacogenes (i.e., genes encoding for enzymes like CYPs or UGTs and transporters like ABC or SLC) on ramipril pharmacokinetic variability and adverse drug reaction (ADR) incidence. Twenty‐nine healthy volunteers who had participated in a single‐dose bioequivalence clinical trial of two formulations of ramipril were recruited. A univariate and multivariate analysis searching for associations between genetic variants and ramipril pharmacokinetics was performed. SLCO1B1 and ABCG2 genotype‐informed phenotypes strongly predicted ramipril exposure. Volunteers with the SLCO1B1 decreased function (DF) phenotype presented around 1.7‐fold higher dose/weight‐corrected area under the curve (AUC/DW) than volunteers with the normal function (NF) phenotype (univariate p‐value [puv] 
ISSN:1742-7835
1742-7843
1742-7843
DOI:10.1111/bcpt.14046