中国房颤患者利伐沙班浓度与常规凝血筛查试验相关性较差

IF 2.1 4区 医学 Q3 PHARMACOLOGY & PHARMACY
Jiake He, Bo Zhu, Yang Shen, Jianping Hu, Kui Hong
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引用次数: 0

摘要

目标本研究的目的是评估中国房颤(AF)患者用金标准定量的利伐沙班血药浓度与常规凝血试验测定的抗凝活性之间的关系。这些试验的正常结果是否可靠,以排除临床相关的利伐沙班水平在不同的阈值也进行了探讨。进一步评价临床药物相互作用(ddi)对利伐沙班暴露及抗凝效果的影响。方法:116例接受利伐沙班治疗的非瓣膜性房颤患者。采用超高效液相色谱-串联质谱(UPLC-MS/MS)和血液凝固分析仪分别测定利伐沙班浓度和凝血试验。结果。谷浓度(Ctrough)与凝血酶原时间(PT)或国际归一化比(INR)相关性中等,Spearman相关系数分别为0.495和0.506。正常PT/INR不能排除30 ng/mL和50 ng/mL,但阴性预测值达到100%,排除100 ng/mL。cough与活化的部分凝血活素时间(aPTT)相关性较小(Spearman相关系数为0.241),与凝血酶时间(TT)无相关性(Spearman相关系数为0.074)。无论是aPTT还是TT都不能准确预测任何浓度下的穿透。峰浓度(Cpeak)与凝血参数无关。地高辛和非布司他的存在使利伐沙班的剂量增加了2.18倍,PT和INR分别延长了44.16%和43.60%。结论。正常常规凝血试验不足以监测利伐沙班治疗。在中国房颤患者中,利伐沙班浓度与常规凝血检测的相关性较差。单独使用地高辛/非布司他对利伐沙班浓度没有影响;然而,联合强乳腺癌耐药蛋白抑制剂(非布司他)和p -糖蛋白探针(地高辛)在肾功能损害患者中,利伐沙班可能导致临床显著的DDI。在临床实践中建立利伐沙班的常规治疗药物监测还需要更多的研究。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Poor Correlation of Rivaroxaban Concentration with the Routine Coagulation Screening Test in Chinese Patients with Atrial Fibrillation
Aims. The aim of this study is to assess the relationship between rivaroxaban plasma concentration quantified by the gold standard and anticoagulant activities measured by routine coagulation assays in Chinese atrial fibrillation (AF) patients. Whether the normal results of these tests were reliable to rule out clinically relevant rivaroxaban levels at various thresholds was also explored. The effect of clinical drug-drug interactions (DDIs) on the exposure and anticoagulant effect of rivaroxaban were further evaluated. Methods. 116 patients receiving rivaroxaban for the management of nonvalvular AF were recruited. Rivaroxaban concentrations and coagulation tests were measured by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) and a blood coagulation analyzer, respectively. Results. The correlation of trough concentration (Ctrough) and prothrombin time (PT) or international normalized ratio (INR) was moderate with Spearman’s correlation coefficient of 0.495 and 0.506, respectively. A normal PT/INR was unable to rule out Ctrough levels of >30 ng/mL and >50 ng/mL, but the negative predictive value reached 100% to exclude Ctrough of >100 ng/mL. Ctrough showed a small correlation with activated partial thromboplastin time (aPTT) (Spearman’s correlation coefficient: 0.241) and no correlation with thrombin time (TT) (Spearman’s correlation coefficient: 0.074). Neither aPTT nor TT accurately predicted Ctrough at any concentration. Peak concentration (Cpeak) did not correlate with any coagulation parameters. The presence of digoxin and febuxostat significantly increased rivaroxaban Ctrough by 2.18 fold and prolonged PT and INR by 44.16% and 43.60%, respectively. Conclusions. Normal routine coagulation assays were insufficient to monitor therapy with rivaroxaban. Poor correlations between rivaroxaban concentration and routine coagulation assays were observed in Chinese AF patients. The use of digoxin/febuxostat alone had no effect on rivaroxaban concentrations; however, combined strong breast cancer resistance protein inhibitor (febuxostat) and P-glycoprotein probe (digoxin) in patients with renal impairment is likely to cause clinically significant DDI with rivaroxaban. More studies are needed to establish routine therapeutic drug monitoring of rivaroxaban in clinical practice.
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来源期刊
CiteScore
4.10
自引率
5.00%
发文量
226
审稿时长
6 months
期刊介绍: The Journal of Clinical Pharmacy and Therapeutics provides a forum for clinicians, pharmacists and pharmacologists to explore and report on issues of common interest. Reports and commentaries on current issues in medical and pharmaceutical practice are encouraged. Papers on evidence-based clinical practice and multidisciplinary collaborative work are particularly welcome. Regular sections in the journal include: editorials, commentaries, reviews (including systematic overviews and meta-analyses), original research and reports, and book reviews. Its scope embraces all aspects of clinical drug development and therapeutics, including: Rational therapeutics Evidence-based practice Safety, cost-effectiveness and clinical efficacy of drugs Drug interactions Clinical impact of drug formulations Pharmacogenetics Personalised, stratified and translational medicine Clinical pharmacokinetics.
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