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Approaches to predicting the efficacy and safety of amlodipine in patients with arterial hypertension of I–II degree based on pharmacogenetic studies

[Original research]
Dmitry Sychev; Evgeniya Shih; Tatiana Evgenyevna Morozova; Artur Damirovich Ismagilov; Evgeniya Shih; Karin Badavievich Mirzaev; Sarvinoz Sharafidinovna Atakulova;

At the study conducted of increase the efficacy and safety of therapy in patients with arterial hypertension (AH) of I–II degree by personalizing the choice of amlodipine dosage regimen based on genotyping by ABCВ1, CYP3A5, and phenotyping by CYP3A4. Clinical and pharmacogenetic study of amlodipine was conducted with 100 patients with arterial hypertension I–II degree between the ages of 42 to 58, (m – 45 %, f – 55 %). The «SNP-Screen» set («Sintol», Russia) was used to determine the polymorphism of the CYP3A5 gene. The metabolic activity of the CYP3A4 isoenzyme was determined by high-performance liquid chromatography (HPLC). The metabolic activity of CYP3A4 was calculated from the 6-beta-hydroxycortisol/cortisol ratio in the morning urine. Our study showed associations between the CYP3A5 gene from the polymorphic marker A6986G and the safety profile of amlodipine, and the lack of significant influence of the course of amlodipine on CYP3A4 activity. In the AG genotype of the CYP3A5 gene, higher antihypertensive efficacy is associated with a higher risk of developing ADR, whereas in the GG genotype – lower efficacy and less risk of developing ADR. The activity of CYP3A4 does not change with the background use of amlodipine (p=0.06). The obtained pharmacogenetic data make it possible to propose an algorithm for personalized choice of the dosage regimen of amlodipine for patients with an AH I–II degree.

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Keywords: pharmacogenetics, personalized medicine, gene polymorphisms, arterial hypertension, amlodipine


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