The Influence of the CES1 Genotype on the Pharmacokinetics of Enalapril in Patients with Arterial Hypertension

The angiotensin-converting enzyme inhibitor enalapril is hydrolysed to an active metabolite, enalaprilat, in the liver via carboxylesterase 1 (CES1). Previous studies show that variant rs71647871 in the CES1 gene affects the pharmacokinetics of enalapril on liver samples as well as healthy volunteer...

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Published inJournal of personalized medicine Vol. 12; no. 4; p. 580
Main Authors Ikonnikova, Anna, Rodina, Tatiana, Dmitriev, Artem, Melnikov, Evgeniy, Kazakov, Ruslan, Nasedkina, Tatiana
Format Journal Article
LanguageEnglish
Published Switzerland MDPI AG 05.04.2022
MDPI
Subjects
Angiotensin
Angiotensin-converting enzyme inhibitors
Antihypertensives
Blood pressure
Body mass index
Carboxylesterase
Drug dosages
Enzymes
Gender
Genetic markers
Genotypes
Heart failure
Heterozygotes
High-performance liquid chromatography
Homozygotes
Hypertension
Liver
Patients
Peptidyl-dipeptidase A
Pharmacokinetics
Precision medicine
Regression analysis
Single-nucleotide polymorphism
Statistical analysis
Variables
United States > US
Russia
SNP
carboxylesterase 1
enalapril
hypertension
cardiology
pharmacogenetics
CES1
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Summary:The angiotensin-converting enzyme inhibitor enalapril is hydrolysed to an active metabolite, enalaprilat, in the liver via carboxylesterase 1 (CES1). Previous studies show that variant rs71647871 in the CES1 gene affects the pharmacokinetics of enalapril on liver samples as well as healthy volunteers. This study included 286 Caucasian patients with arterial hypertension who received enalapril. The concentrations of enalapril and enalaprilat were determined before subsequent intake of the drug and 4 h after it with high-performance liquid chromatography (HPLC) and mass spectrometric detection. The study included genetic markers as follows: rs2244613, rs71647871 (c.428G>A, p.G143E) and three SNPs indicating the presence of a subtype CES1A1c (rs12149368, rs111604615 and rs201577108). Mean peak and trough enalaprilat concentrations, adjusted by clinical variables, were significantly lower in CES1 rs2244613 heterozygotes (by 16.6% and 19.6%) and in CC homozygotes (by 32.7% and 41.4%) vs. the AA genotype. In CES1A1c homozygotes, adjusted mean enalaprilat concentrations were 75% lower vs. heterozygotes and wild-type (WT) homozygotes. Pharmacogenetic markers of the CES1 gene may be a promising predictor for individualisation when prescribing enalapril.
ISSN:2075-4426
2075-4426
DOI:10.3390/jpm12040580