接受R-CHOP免疫化疗的弥漫大B细胞淋巴瘤成人患者服用利伐沙班和达比加群后的药效学研究

IF 4.9 3区 医学 Q1 PHARMACOLOGY & PHARMACY Pharmaceutics Pub Date : 2024-10-11 DOI:10.3390/pharmaceutics16101319
Teerachat Punnachet, Tim R Cressey, Porntipa Apiwatnakorn, Atisa Koonarat, Lalita Norasetthada, Adisak Tantiworawit, Ekarat Rattarittamrong, Thanawat Rattanathammethee, Sasinee Hantrakool, Pokpong Piriyakhuntorn, Nonthakorn Hantrakun, Piangrawee Niprapan, Chatree Chai-Adisaksopha
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引用次数: 0

摘要

背景/目的:利伐沙班和达比加群常被用于治疗活动期癌症患者的血栓栓塞性疾病。然而,有关同期化疗对直接口服抗凝药(DOAC)药效学影响的研究却十分有限。我们的研究旨在评估利伐沙班和达比加群联合化疗对弥漫大 B 细胞淋巴瘤(DLBCL)患者药效学的影响:这是一项前瞻性药效学研究。符合条件的受试者年龄≥18 岁,确诊为 DLBCL 并开始接受 R-CHOP(利妥昔单抗、环磷酰胺、多柔比星、长春新碱和泼尼松)免疫化疗。入组成人接受利伐沙班(10 毫克,每天一次)或达比加群依替沙拉特(110 毫克,每天两次)治疗。在服用 R-CHOP 之前和之后的给药间隔期间,对服用利伐沙班的参与者的血浆抗因子 Xa (FXa) 和服用达比加群的参与者的稀释凝血酶时间 (dTT) 进行了评估。采用非室分析法确定利伐沙班和达比加群的药效学参数:26名成人参加了研究,其中利伐沙班组12人,达比加群组14人。平均年龄为 59 ± 14.4 岁。利伐沙班组的 FXa 抑制AUEC 在 R-CHOP 后无显著变化(平均差异 3.8 ng-h/mL,95% 置信区间 (CI) -155.4 至 163.0,p = 0.96)。同样,在达比加群组中,R-CHOP 后 dTT 的 AUEC 保持不变(平均差 54.41 ng-h/mL,95% CI -99.09 至 207.9 ng/mL,p = 0.46)。然而,与未接受 R-CHOP 化疗的患者(4 小时,[最小-最大值,3-8],p = 0.04)相比,接受 R-CHOP 化疗的患者的 dTT 达到峰值的中位时间明显更快(3 小时,[最小-最大值,1.5-8]);结论:R-CHOP 化疗后,患者的 dTT 达到峰值的中位时间明显更快:同时接受 R-CHOP 化疗对利伐沙班的 FXa 抑制作用和达比加群的 dTT 作用没有明显影响。达比加群与 R-CHOP 同时用药时,达峰值 dTT 的时间更快。
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Pharmacodynamics of Rivaroxaban and Dabigatran in Adults with Diffuse Large B-Cell Lymphoma Receiving R-CHOP Immunochemotherapy.

Background/Objectives: Rivaroxaban and dabigatran are commonly used for thromboembolic disease management in active cancer patients. However, limited research explores the impact of concurrent chemotherapy on the pharmacodynamics of direct oral anticoagulants (DOAC). The aim of our study was to evaluate the impact of combined chemotherapy with rivaroxaban and dabigatran on the pharmacodynamics in patients with diffuse large B-cell lymphoma (DLBCL).; Methods: This was a prospective, pharmacodynamic study. Eligible subjects were ≥18 years old, diagnosed with DLBCL and initiating R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) immunochemotherapy. The enrolled adults received either rivaroxaban (10 mg once daily) or dabigatran etixalate (110 mg twice daily). Plasma anti-factor Xa (FXa) in participants on rivaroxaban and diluted thrombin time (dTT) in participants on dabigatran were assessed over the dosing interval before and after R-CHOP administration. Pharmacodynamic parameters of rivaroxaban and dabigatran were determined using a non-compartmental analysis.; Results: Twenty-six adults participated, with twelve in the rivaroxaban group and fourteen in the dabigatran group. The mean age was 59 ± 14.4 years. In the rivaroxaban group, the AUEC of FXa inhibition showed no significant change after R-CHOP (mean difference 3.8 ng·h/mL, 95% confidence interval (CI) -155.4 to 163.0, p = 0.96). Similarly, in the dabigatran group, the AUEC of dTT remained unchanged post R-CHOP (mean difference 54.41 ng·h/mL, 95% CI -99.09 to 207.9 ng/mL, p = 0.46). However, the median time-to-peak dTT was significantly faster with R-CHOP (3 h, [min-max, 1.5-8] compared to without it (4 h, [min-max, 3-8], p = 0.04); Conclusions: Concurrent R-CHOP chemotherapy did not significantly impact FXa inhibition by rivaroxaban or dTT by dabigatran. The time-to-peak dTT was faster when dabigatran was administered with R-CHOP.

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来源期刊
Pharmaceutics
Pharmaceutics Pharmacology, Toxicology and Pharmaceutics-Pharmaceutical Science
CiteScore
7.90
自引率
11.10%
发文量
2379
审稿时长
16.41 days
期刊介绍: Pharmaceutics (ISSN 1999-4923) is an open access journal which provides an advanced forum for the science and technology of pharmaceutics and biopharmaceutics. It publishes reviews, regular research papers, communications,  and short notes. Covered topics include pharmacokinetics, toxicokinetics, pharmacodynamics, pharmacogenetics and pharmacogenomics, and pharmaceutical formulation. Our aim is to encourage scientists to publish their experimental and theoretical details in as much detail as possible. There is no restriction on the length of the papers. The full experimental details must be provided so that the results can be reproduced.
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