Effect of CYP4F2 Polymorphisms on Ticagrelor Pharmacokinetics in Healthy Chinese Volunteers

Nie, Shanshan; Chen, Kaifeng; Guo, Chengxian; Pei, Qi; Zou, Chan; Yao, Liangyuan; Yuan, Hang; Zhao, Xia; Xie, Ran; He, Xu; Huang, Jie; Yang, Guoping

doi:10.3389/fphar.2021.797278

Cited by 6 publications

(4 citation statements)

References 37 publications

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“…The TT genetic variant was more common among those patients who reported bleeding events within a 3-month period after hospitalization [19]. Nie et al observed that the CYP4F2 gene polymorphism had a remarkable effect on the pharmacokinetic parameters of ticagrelor [18]. The findings of our study did not show any association between the occurrence of dyspnea and CYP4F2 variants.…”

Section: Discussioncontrasting

confidence: 58%

“…An analysis of the literature related to ticagrelor has revealed that different enzymes may be involved in determining the therapeutic effect of ticagrelor. Nie et al showed that CYP4F2 rs2074900 had an effect on the pharmacokinetics of ticagrelor [18]. Our previous studies showed [16,19] that CYP4F2 variants may determine bleeding during ticagrelor therapy.…”

Section: Introductionmentioning

confidence: 78%

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Factors Determining Ticagrelor-Induced Dyspnea in Patients with Acute Coronary Syndrome

et al. 2022

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(1) Background: The aim of this study was to determine clinical and genetic factors predicting the development of dyspnea in patients receiving ticagrelor. (2) Methods: A total of 277 patients with acute myocardial infarction (with and without ST-segment elevation), who underwent coronary angiography and PTCA with stent implantation and treated with antiplatelet drugs (ticagrelor and aspirin), were enrolled in this study. Platelet aggregation (induction with high-sensitivity ADP, ADP HS) testing was performed using a MULTIPLATE analyzer and reagents for the determination of P2Y12 receptor activity. Venous blood samples were collected for genotyping. (3) Results: Patients experiencing ticagrelor-related dyspnea had lower ADP HS. ROC curve analysis showed that an ADP HS cut-off of ≤19.5 U was associated with the development of dyspnea. The ADP HS value of ≤19.5 U and any dose of atorvastatin lower than 80 mg (or no atorvastatin) increased the risk of dyspnea by more than 4 and 2 times, respectively (OR = 4.07, p ≤ 0.001 and OR = 2.25; p = 0.008). (4) Conclusion: A lower ADP HS value possibly indicates greater ticagrelor activity and a higher plasma concentration of this drug. Atorvastatin might have an impact on the occurrence of ticagrelor-related dyspnea by affecting ticagrelor metabolism. No impact of any genetic variant on the development of dyspnea was determined.

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Section: Discussioncontrasting

confidence: 58%

Section: Introductionmentioning

confidence: 78%

Factors Determining Ticagrelor-Induced Dyspnea in Patients with Acute Coronary Syndrome

et al. 2022

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“…Next, we coated a nanopore pipette with PBA via AuÀ S bonds and measured the VCM concentration from the ion current. There are many high-risk drugs that contain diols, such as digoxin and ticagrelor [40][41][42]. This method may be suitable for simple, rapid quantification of drugs including VCM.…”

Section: Discussionmentioning

confidence: 99%

Vancomycin sensing using a phenylboronic acid‐modified nanopore pipette

Sato

Nakano

et al. 2023

Electroanalysis

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Nanopore sensing measures the changes in charge and physical state around the nanopores as changes in ionic current. In this study, we performed vancomycin (VCM) sensing with nanopores modified via Au−S bonds with dithiobis(4‐butyrylamino‐m‐phenylboronic acid) (DTBA‐PBA), a derivative of phenylboronic acid (PBA) bearing a thiol. First, we modified a 3‐mm‐diameter Au electrode with a DTBA‐PBA self‐assembled monolayer (SAM) to confirm the VCM response of the PBA interface by cyclic voltammetry. DTBA‐PBA was then immobilized in the same manner on a nanopore pipette coated with an Au layer. We measured the VCM concentration from the change in ion current using the nanopore pipette. A VCM concentration‐dependent ionic current response was observed in the range of 0.01–1 mM. Many kinds of pharmaceuticals can bind to PBA; therefore, this method could be used for quick, easy, in situ quantification of not only VCM but also other pharmaceuticals with serious side effects.

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“…Yet, another study found no effect of CYP3A4/3A5 or SLCO1B1 genotype [42], although a subsequent study implicated a separate variant of CYP3A4 (rs35599367) to markedly impair ticagrelor elimination [43]. More recently, Nie et al analyzed associations between 35 variants (not including CYP3A4 rs35599367) across 10 genes in a study of 68 healthy Chinese volunteers [44]. They found no association with SLCO1B1, UGT2B7, or CYP3A4/3A5 genotype but reported homozygotes of the CYP4F2 rs2074900 variant, commonly found in East Asian populations, to substantially increase peak drug concentration and total drug exposure.…”

Section: Ticagrelormentioning

confidence: 99%

Personalized Dual Antiplatelet Therapy in Acute Coronary Syndromes: Striking a Balance Between Bleeding and Thrombosis

et al. 2023

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Purpose of Review Dual antiplatelet therapy (DAPT)—aspirin in conjunction with a P2Y12 inhibitor—is the cornerstone of managing patients with acute coronary syndromes post-revascularization, but the clinical response is highly variable, with potentially devastating consequences. Herein, we review the mechanisms underpinning said variability and explore emerging approaches to normalizing therapeutic benefit. Recent Findings. The potent P2Y12 inhibitors, prasugrel and ticagrelor, exhibit minimal inter-individual variability, replacing clopidogrel in DAPT and achieving greater rates of therapeutic response. However, these benefits decline in later phases when bleeding risk begins to supersede that of ischemia. Guided de-escalation of P2Y12 inhibition as well as shortening DAPT duration have emerged as strategies that retain antithrombotic efficacy while reducing bleeding risk. Aspirin is the other component of DAPT but is also used in isolation for secondary prevention of thrombotic disease. In contrast to the P2Y12 inhibitors, genetic influences on aspirin non-response appear to be outweighed by a triad of clinical factors: non-adherence, enteric aspirin use, and inappropriate dosing according to bodyweight and BMI. Summary Multiple de-escalation strategies for DAPT have been shown to mitigate bleeding risk, but it remains unclear which approach is ideal, necessitating head-to-head investigations to determine which exhibits the most favorable cost-to-benefit ratio. However, there is likely a role for more than one approach in clinical practice, depending on patient risk profile. Our approach to aspirin use is also in need of reassessment: strategies to improve adherence, avoidance of enteric aspirin in cardiac patients, and dose adjustment according to bodyweight and/or BMI are all likely to improve rates of therapeutic response. Moreover, platelet function testing may have a role in identifying patients expected to benefit from primary prophylactic aspirin.

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Effect of CYP4F2 Polymorphisms on Ticagrelor Pharmacokinetics in Healthy Chinese Volunteers

Cited by 6 publications

References 37 publications

Factors Determining Ticagrelor-Induced Dyspnea in Patients with Acute Coronary Syndrome

Factors Determining Ticagrelor-Induced Dyspnea in Patients with Acute Coronary Syndrome

Vancomycin sensing using a phenylboronic acid‐modified nanopore pipette

Personalized Dual Antiplatelet Therapy in Acute Coronary Syndromes: Striking a Balance Between Bleeding and Thrombosis

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