An analysis on distribution and inter-relationships of biomarkers under rivaroxaban in Japanese patients with non-valvular atrial fibrillation (CVI ARO 1)

Suzuki, Shinya; Yamashita, Takeshi; Kasai, Hidefumi; Otsuka, Takayuki; Sagara, Koichi

doi:10.1016/j.dmpk.2018.02.002

Cited by 17 publications

(34 citation statements)

References 29 publications

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“…Rivaroxaban was among the top 10 drugs involved in emergency department visits for adverse drug events in the United States in 2013‐2014 5 . In addition, interindividual variability of the pharmacokinetics of rivaroxaban in patients with NVAF has been shown to be large 6‐9 …”

Section: Introductionmentioning

confidence: 99%

Impact of gene polymorphisms in drug‐metabolizing enzymes and transporters on trough concentrations of rivaroxaban in patients with atrial fibrillation

Nakagawa

Kinjo

Iizuka

et al. 2020

Basic Clin Pharma Tox

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Direct oral anticoagulants (DOACs) are increasingly used in clinical practice to prevent venous thrombosis or thrombus formation in non-valvular atrial fibrillation (NVAF). 1 The usage of rivaroxaban, a factor Xa (FXa) inhibitor, increased from 0.13% to 13.87% from 2011 to 2014 in the United States of America (USA). 2 Rivaroxaban has been shown to have efficacy similar to that of warfarin for prevention of stroke or systemic embolism in patients with NVAF. 3 In addition, fatal bleeding and intracranial haemorrhage occur less frequently in patients receiving rivaroxaban than in those receiving warfarin. 3 Although DOACs do not require routine coagulation monitoring, serious bleeding events have been occasionally reported in patients taking these drugs. 4 Rivaroxaban was among the top 10 drugs involved in emergency department visits for adverse drug events in the United States in 2013-2014. 5 In addition, interindividual variability of the pharmacokinetics of rivaroxaban in patients with NVAF has been shown to be large. 6-9

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Section: Introductionmentioning

confidence: 99%

Impact of gene polymorphisms in drug‐metabolizing enzymes and transporters on trough concentrations of rivaroxaban in patients with atrial fibrillation

Nakagawa

Kinjo

Iizuka

et al. 2020

Basic Clin Pharma Tox

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“…The data obtained by us on the interindividual variability of the pharmacokinetics of rivaroxaban in patients with atrial fibrillation correlate with a number of scientific studies [30–32].…”

Section: Discussionmentioning

confidence: 73%

Influence of ABCB1, CYP3A5 and CYP3A4 gene polymorphisms on prothrombin time and the residual equilibrium concentration of rivaroxaban in patients with non-valvular atrial fibrillation in real clinical practice

Сычев

Соколов

Reshetko

et al. 2022

Pharmacogenetics and Genomics

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Objective The study of ABCB1 and CYP3A4/3A5 gene polymorphism genes is promising in terms of their influence on prothrombin time variability, the residual equilibrium concentration of direct oral anticoagulants (DOACs) in patients with atrial fibrillation and the development of new personalized approaches to anticoagulation therapy in these patients. The aim of the study is to evaluate the effect of ABCB1 (rs1045642) C>T; ABCB1 (rs4148738) C>T and CYP3A5 (rs776746) A>G, CYP3A4*22(rs35599367) C>T gene polymorphisms on prothrombin time level and residual equilibrium concentration of rivaroxaban in patients with atrial fibrillation. Methods In total 86 patients (42 men and 44 female), aged 67.24 ± 1.01 years with atrial fibrillation were enrolled in the study. HPLC mass spectrometry analysis was used to determine rivaroxaban residual equilibrium concentration. Prothrombin time data were obtained from patient records. Results The residual equilibrium concentration of rivaroxaban in patients with ABCB1 rs4148738 CT genotype is significantly higher than in patients with ABCB1 rs4148738 CC (P = 0.039). The analysis of the combination of genotypes did not find a statistically significant role of combinations of alleles of several polymorphic markers in increasing the risk of hemorrhagic complications when taking rivaroxaban. Conclusion Patients with ABCB1 rs4148738 CT genotype have a statistically significantly higher residual equilibrium concentration of rivaroxaban in blood than patients with ABCB1 rs4148738 CC genotype, which should be considered when assessing the risk of hemorrhagic complications and risk of drug–drug interactions. Further studies of the effect of rivaroxaban pharmacogenetics on the safety profile and efficacy of therapy are needed.

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“…There is no reference range for the number of patients and sample size for population PK and PK-PD studies. Referring to the sample size in previous studies,13 31 32 we aim to enrol at least 50 outpatients and 150 inpatients in total. In view of the reality that the timing of medication administration and adherence is better controlled for inpatients, only the data from inpatients will be used to perform population PK-PD analysis.…”

Section: Methodsmentioning

confidence: 99%

“…Data from previous clinical trials and real-world studies have been used to develop a population pharmacokinetic (PK) or pharmacokinetic-pharmacodynamic (PK-PD) model of rivaroxaban to quantify the variation in PK and/or PD in NVAF patients 10–13. The standard rivaroxaban dose for Caucasian NVAF patients was 20 mg, whereas 15 mg was selected for Japanese patients on account of the model-based PK studies, which showed an equivalent exposure for Japanese patients taking 15 mg and Caucasian patients taking 20 mg 12.…”

Section: Introductionmentioning

confidence: 99%

Rationale and design of a prospective study evaluating population pharmacokinetics and pharmacodynamics of rivaroxaban in Chinese patients with non-valvular atrial fibrillation

et al. 2022

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IntroductionRivaroxaban is one of the most commonly used non-vitamin K antagonists for stroke prevention in patients with non-valvular atrial fibrillation (NVAF). Different individual exposures exist for Asian and non-Asian populations, and dose selection is different for Japanese and non-Japanese subjects. Few studies have investigated the pharmacokinetics (PK) and pharmacodynamics (PD) of rivaroxaban in Chinese patients and provided a solid reference for dose selection and individualised therapy.Methods and analysisThis is a single-centre prospective study. Rivaroxaban-treated Chinese NVAF patients will be recruited according to predetermined inclusion criteria. Blood samples will be collected from both outpatients and inpatients with different sampling strategies at steady state. Rivaroxaban plasma concentration, factor Xa activity, prothrombin time and single-nucleotide polymorphisms of candidate genes will be evaluated. Follow-up will be conducted following 3 and 6 months after enrolment to collect information about the safety and efficacy outcomes. A nonlinear mixed-effects modelling strategy will be used to develop a population PK-PD model of rivaroxaban.Ethics and disseminationThe study has been approved by the Ethics Committee of Huashan Hospital, Fudan University (KY2020-016). The study findings will be submitted to peer-reviewed journals and shared with public health authorities.Trial registration numberChiCTR2100046685.

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An analysis on distribution and inter-relationships of biomarkers under rivaroxaban in Japanese patients with non-valvular atrial fibrillation (CVI ARO 1)

Cited by 17 publications

References 29 publications

Impact of gene polymorphisms in drug‐metabolizing enzymes and transporters on trough concentrations of rivaroxaban in patients with atrial fibrillation

Impact of gene polymorphisms in drug‐metabolizing enzymes and transporters on trough concentrations of rivaroxaban in patients with atrial fibrillation

Influence of ABCB1, CYP3A5 and CYP3A4 gene polymorphisms on prothrombin time and the residual equilibrium concentration of rivaroxaban in patients with non-valvular atrial fibrillation in real clinical practice

Rationale and design of a prospective study evaluating population pharmacokinetics and pharmacodynamics of rivaroxaban in Chinese patients with non-valvular atrial fibrillation

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