ArticleBiochemical pharmacology2016
Dabigatran etexilate activation is affected by the CES1 genetic polymorphism G143E (rs71647871) and gender.
Article in Biochemical pharmacology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 3 registered trials, which are not on this map. Cited by 52 papers, 3 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Investigation of Genetic Variations on Patients With Adverse Drug Events While on Direct Oral Anticoagulants (DOACs)
Investigation of Genetic Variations on Patients With Adverse Events While on Direct Oral Anticoagulants (DOACs)
Correlation Between Bleeding Complication and Treatment Failure of DOAC and Its Predictions Based on Cipherome's Pharmacogenomic Technology
Who cites it
52 citing papers in PubMed, 3 syntheses or guidelines pooled it, 107 citations in OpenAlex.
- The role of ABCB1 and CES1 genotypes on the efficacy and safety of dabigatran: a systematic review and meta-analysis.Human genomics · 2025Pooled it
- Optimal management of cardiac surgery patients using direct oral anticoagulants: recommendations for clinical practice.European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery · 2023Pooled it
- Association betweenFrontiers in cardiovascular medicine · 2022Pooled it
- Randomized evaluation of the loss-of-function carboxylesterase 1 (CES1) G143E variant on clopidogrel and ticagrelor pharmacodynamics.Clinical and translational science · 2024Trial
- Impact of carboxylesterase 1 genetic polymorphism on trandolapril activation in human liver and the pharmacokinetics and pharmacodynamics in healthy volunteers.Clinical and translational science · 2021Trial
- The Impact of ABCB1 and CES1 Polymorphisms on Dabigatran Pharmacokinetics in Healthy Chinese Subjects.Pharmacogenomics and personalized medicine · 2021Trial
- Sex-related differences in blood concentrations and emergence profiles following total intravenous anesthesia with remimazolam and remifentanil.Scientific reports · 2026Observational
- Biological sex differences in pharmacokinetics and adverse drug reactions.Naunyn-Schmiedeberg's archives of pharmacology · 2026Review
- Sex differences in the response to treatment of attention deficit hyperactivity disorder.Naunyn-Schmiedeberg's archives of pharmacology · 2026Review
- Pharmacogenomics in the prediction of adverse effects of cardiovascular drugs: the PGx-CardioDrug project.Croatian medical journal · 2026Review
- Flumazenil reversal of remimazolam-induced sedation: a narrative review of safety, pharmacokinetics, and clinical considerations.Frontiers in medicine · 2026Review
- Clinical Application of Pharmacogenomics in Stroke Management: Current Evidence and Future Directions.Journal of stroke · 2026Review
- Sex differences in hepatic enzymes and transporters involved in pharmacokinetics.Liver research (Beijing, China) · 2025Review
- An in vitro evaluation of common botanical extracts on carboxylesterase 1 catalytic activity.Drug metabolism and disposition: the biological fate of chemicals · 2025Article
- Idarucizumab more effectively reverses the anticoagulant effects of dabigatran acylglucuronide than dabigatran.Scientific reports · 2025Article
- Regulation of Human Hydrolases and Its Implications in Pharmacokinetics and Pharmacodynamics.Drug metabolism and disposition: the biological fate of chemicals · 2024Review
- Pharmacogenetic study of CES1 gene and enalapril efficacy.Journal of applied genetics · 2024Review
- Circulating microRNAs and DNA Methylation as Regulators of Direct Oral Anticoagulant Response in Atrial Fibrillation and Key Elements for the Identification of the Mechanism of Action (miR-CRAFT): Study Design and Patient Enrolment.Journal of personalized medicine · 2024Article
- Regulation of carboxylesterases and its impact on pharmacokinetics and pharmacodynamics: an up-to-date review.Expert opinion on drug metabolism & toxicology · 2024Review
- Role ofJournal of clinical medicine · 2024Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
The oral anticoagulant prodrug dabigatran etexilate (DABE) is sequentially metabolized by intestinal carboxylesterase 2 (CES2) and hepatic carboxylesterase 1 (CES1) to form its active metabolite dabigatran (DAB). A recent genome-wide association study reported that the CES1 single nucleotide polymorphisms (SNPs) rs2244613 and rs8192935 were associated with lower DAB plasma concentrations in the Randomized Evaluation of Long-term Anticoagulation Therapy (RE-LY) study participants. In addition, gender differences in exposure to DAB were observed in clinical studies. The aim of this study was to examine the effect of CES1 genetic polymorphisms and gender on DABE activation using several in vitro approaches. The genotypes of the CES1 SNPs rs2244613, rs8192935, and the known loss-of-function CES1 variant rs71647871 (G143E), and the activation of DABE and its intermediate metabolites M1 and M2 were determined in 104 normal human liver samples. DABE, M1, and M2 activations were found to be impaired in human livers carrying the G143E variant. However, neither rs2244613 nor rs8192935 was associated with the activation in human livers. The incubation study of DABE with supernatant fractions (S9) prepared from the G143E-transfected cells showed that the G143E is a loss-of-function variant for DABE metabolism. Moreover, hepatic CES1 activity on M2 activation was significantly higher in female liver samples than male. Our data suggest that CES1 genetic variants and gender are important contributing factors to variability in DABE activation in humans. A personalized DABE treatment approach based on patient-specific CES1 genotypes and sex may have the potential to improve the efficacy and safety of DABE pharmacotherapy.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.