The impact of ABCB1, CYP3A4 and CYP3A5 gene polymorphisms on apixaban trough concentration and bleeding risk in patients with atrial fibrillation.
Drug Metab Pers Ther
; 39(2): 89-97, 2024 Jun 01.
Article
em En
| MEDLINE
| ID: mdl-38943286
ABSTRACT
OBJECTIVES:
Apixaban, a direct oral anticoagulant, is increasingly used worldwide for the treatment and prevention of venous thromboembolism and ischemic stroke in patients with nonvalvular atrial fibrillation (AF). Obviously, one of the ways to enhance effectiveness and safety of drug therapy is a personalized approach to therapy, which involves pharmacogenetic and pharmacokinetic tests. The study aims to investigate the effect of CYP3A4*22, CYP3A5*3 and ABCB1 polymorphisms on the pharmacokinetics of apixaban and the risk of bleeding.METHODS:
A total of 84 patients were enrolled in this prospective observational study. All patients received apixaban 5 or 2.5â¯mg twice daily. Real-time polymerase chain reaction was used to evaluate single-nucleotide polymorphisms of the ABCB1 gene (rs1045642 and rs4148738), CYP3A4*22 (rs35599367) C>T, CYP3A5*3 (rs776746) A>G. A plasma trough concentration/dose (C/D) ratio was used as a pharmacokinetic index.RESULTS:
The C/D ratio was higher in patients aged >80 years (F(1)=11.209, p=0.00124) and was affected by serum creatinine (>133⯵mol/L, F(1)=6.7, p=0.01124). ABCB1 (rs1045642 and rs4148738), CYP3A5 (rs776746) and CYP3A4 (rs35599367) polymorphisms did not show a correlation with C/D ratio of apixaban. Multivariate logistic regression analyses showed that none of the clinical or genetic factors predicted the fact of bleeding.CONCLUSIONS:
We report no significant association between ABCB1 gene polymorphisms (rs1045642 and rs4148738), CYP3A4*22 (rs35599367) C>T, CYP3A5*3 (rs776746) A>G and bleeding events on apixaban treatment. Complementing the existing criteria with pharmacogenetic and pharmacokinetics information for the patients with AF will enable further individualization of apixaban.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Pirazóis
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Piridonas
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Fibrilação Atrial
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Subfamília B de Transportador de Cassetes de Ligação de ATP
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Polimorfismo de Nucleotídeo Único
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Citocromo P-450 CYP3A
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Hemorragia
Limite:
Aged
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Aged80
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Drug Metab Pers Ther
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Drug Metab. Pers. Ther
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Drug metabolism and personalized therapy (Internet)
Ano de publicação:
2024
Tipo de documento:
Article