SLCO1B1 and ABCG2 genotype-informed phenotypes are related to variation in ramipril exposure.
Basic Clin Pharmacol Toxicol
; 135(3): 295-307, 2024 Sep.
Article
en En
| MEDLINE
| ID: mdl-39011815
ABSTRACT
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] < 0.001, multivariate p-value [pmv] < 0.001, ß = 0.533, R2 = 0.648). Similarly, volunteers with ABCG2 DF + poor function (PF) phenotypes presented around 1.6-fold higher AUC/DW than those with the NF phenotype (puv = 0.011, pmv < 0.001, ß = 0.259, R2 = 0.648). Our results suggest that SLCO1B1 and ABCG2 are important transporters to ramipril pharmacokinetics, and their genetic variation strongly alters its pharmacokinetics. Further studies are required to confirm these associations and their clinical relevance.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Fenotipo
/
Inhibidores de la Enzima Convertidora de Angiotensina
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Ramipril
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Transportador 1 de Anión Orgánico Específico del Hígado
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Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 2
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Genotipo
/
Proteínas de Neoplasias
Límite:
Adult
/
Female
/
Humans
/
Male
Idioma:
En
Revista:
Basic Clin Pharmacol Toxicol
/
Basic and clinical pharmacology and toxicology
/
Basic clin. pharmacol. toxicol
Asunto de la revista:
FARMACOLOGIA
/
TOXICOLOGIA
Año:
2024
Tipo del documento:
Article
País de afiliación:
España