Efek Polimorfisme Gen Enzim Pemetabolisme Obat terhadap Kadar Rivaroxaban: Sebuah Kajian Naratif
Abstract
Rivaroxaban merupakan agen antikoagulan yang mengalami biotransformasi via liver dengan melibatkan peran dari CYP3A4/5 (18%); CYP2J2 (14%) dan sisanya melalui CYP independent hydrolytic cleavage (14%). Polimorfisme yang terjadi pada gen pemetabolisme obat memengaruhi kadar rivaroxaban di dalam tubuh, hal tersebut telah dilaporkan di dalam berbagai macam penelitian. Kajian naratif ini bertujuan untuk mengulas mengenai pengaruh variasi gen enzim pemetabolisme obat pada kadar rivaroxaban di dalam tubuh pasien dari beberapa penelitian yang sudah dilaporkan. Metode yang digunakan adalah kajian naratif dengan cara menelusuri data berbasis Google Scholar dengan kata kunci rivaroxaban, polymorphism, CYP3A4, CYP3A5, dan CYP2J2. Beberapa penelitian menunjukan bahwa polimorfisme gen pemetabolisme tidak memberikan pengaruh yang signifikan terhadap perubahan kadar rivaroxaban di dalam darah, namun masih terdapat beberapa keterbatasan penelitian. Perlu adanya penelitian yang lebih komprehensif dengan melibatkan keseluruhan single nucleotide polymorphism (SNP) yang berperan dalam farmakokinetika rivaroxaban, mengingat rivaroxaban dimetabolisme oleh beberapa isoenzim CYP dan diekskersikan oleh beberapa transporter, sehingga hal tersebut masih membuka kesempatan untuk penelitian lebih lanjut mengenai farmakogenomik rivaroxaban.
Kata kunci: CYP3A4, CYP3A5, CYP2J2, polimorfisme, rivaroxaban
Effect of Gene Polymorphism in Drug-metabolizing Enzyme on Concentration of Rivaroxaban: A Narrative Review
Abstract
Rivaroxaban is an anticoagulant agent that often experience biotransformation in the liver through CYP3A4/5 (18%); CYP2J2 (14%) and CYP independent hydrolytic cleavage (14%). Several studies revealed that Polymorphism in drug-metabolizing enzyme genes can affect the rivaroxaban levels in the body. Therefore, this study aims to review the effect of gene variations of metabolizing enzymes on rivaroxaban concentration in patient’s body. A search using keyword rivaroxaban, polymorphism, CYP3A4, CYP3A5 and CYP2J2 was carried out in Google Scholar. Several studies showed that polymorphisms of metabolizing genes do not have a significant effect on rivaroxaban concentration. There is also a need for comprehensive studies involving all single nucleotide polymorphisms (SNPs) that play a role in the drug’s pharmacokinetics. This is because rivaroxaban is metabolized by several CYP isoenzymes and excreted by different transporters. This still opens the opportunity for further studies on its pharmacogenomic.
Keywords: CYP3A4, CYP3A5, CYP2J2, polymorphism, rivaroxaban
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DOI: https://doi.org/10.15416/ijcp.2022.11.2.164
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