Pharmacokinetics and Pharmacogenetics of Dabigatran
Open Access
- 3 March 2021
- journal article
- research article
- Published by Silicea - Poligraf in Rational Pharmacotherapy in Cardiology
- Vol. 17 (1), 146-152
- https://doi.org/10.20996/1819-6446-2021-01-04
Abstract
Dabigatran etexilate is a prodrug of dabigatran, a oral direct inhibitor of thrombin. Pharmacokinetics of dabigatran etexilate doesn’t have the disadvantages of vitamin K antagonists. However, pharmacokinetics and pharmacogenetics of dabigatran are variable. This can affect both effectiveness and safety of anticoagulant therapy. It is considered that CES1 enzyme and P-glycoprotein (CES1 and ABCB1 genes accordingly) play important role in pharmacokinetics of dabigatran etexilate. UDP-glucuronosyltransferase enzymes UGT2B15, UGT1A9, UGT2B7 (UGT2B15, UGT1A9, UGT2B7 genes accordingly) take part in the metabolism of active dabigatran. Presence of these gene’s single-nucleotide variants (SNV) can affect effectiveness and safety of dabigatran etexilate usage. The goal of this review is analysis of associated researches of SNV genes CES1 and ABCB1 and search for new candidate genes that reveal effectiveness and safety of dabigatran etexilate usage. Materials and methods. The search for full-text publications in Russian and English languages containing key words “dabigatran etexilate”, “dabigatran”, “pharmacokinetics”, “effectiveness”, “safety” was carried out amongst literature of the past twenty years with the use of eLibrary, PubMed, Web of Science, OMIM data bases. Pharmacokinetics and pharmacogenetics of dabigatran etexilate are considered in this review. The hypothesis about UDP-glucuronosyltransferase enzymes influence on dabigatran metabolism was examined. Nowadays more than 2000 SNV CES1 and ABCB1 genes are identified, but their potential influence on pharmacokinetics of dabigatran etexilate and its active metabolite (dabigatran) in clinical practice needs to be further researched. Role of SNV UDP-glucuronosyltransferase genes (UGT2B15, UGT1A9, UGT2B7) in dabigatran’s effectiveness and safety is not explored enough. However, UGT2B15 gene can be a potential candidate gene for research on safety of this drug.Keywords
This publication has 43 references indexed in Scilit:
- Evaluation of the Impact of UGT Polymorphism on the Pharmacokinetics and Pharmacodynamics of the Novel PPAR Agonist SipoglitazarThe Journal of Clinical Pharmacology, 2013
- Prevention of VTE in Orthopedic Surgery Patients: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice GuidelinesSocial psychiatry. Sozialpsychiatrie. Psychiatrie sociale, 2012
- Oral Anticoagulant Therapy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice GuidelinesSocial psychiatry. Sozialpsychiatrie. Psychiatrie sociale, 2012
- Dabigatran (Pradaxa)American Journal of Neuroradiology, 2012
- Evidence for oxazepam as an in vivo probe of UGT2B15: oxazepam clearance is reduced by UGT2B15 D85Y polymorphism but unaffected by UGT2B17 deletionBritish Journal of Clinical Pharmacology, 2009
- Worldwide stroke incidence and early case fatality reported in 56 population-based studies: a systematic reviewThe Lancet Neurology, 2009
- The pharmacokinetics, pharmacodynamics and tolerability of dabigatran etexilate, a new oral direct thrombin inhibitor, in healthy male subjectsBritish Journal of Clinical Pharmacology, 2007
- Structure, function and regulation of carboxylesterasesChemico-Biological Interactions, 2006
- Cloning of the Human Cholesteryl Ester Hydrolase Promoter: Identification of Functional Peroxisomal Proliferator-Activated Receptor Responsive ElementsBiochemical and Biophysical Research Communications, 2001
- A Comparison of Low-Molecular-Weight Heparin with Unfractionated Heparin for Acute Pulmonary EmbolismThe New England Journal of Medicine, 1997