Punnachet Teerachat, Cressey Tim R, Apiwatnakorn Porntipa, Koonarat Atisa, Norasetthada Lalita, Tantiworawit Adisak, Rattarittamrong Ekarat, Rattanathammethee Thanawat, Hantrakool Sasinee, Piriyakhuntorn Pokpong, Hantrakun Nonthakorn, Niprapan Piangrawee, Chai-Adisaksopha Chatree
Division of Hematology, Department of Internal Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand.
AMS-PHPT Research Collaboration, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai 50200, Thailand.
Pharmaceutics. 2024 Oct 11;16(10):1319. doi: 10.3390/pharmaceutics16101319.
: 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).; : 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.; : 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, = 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, = 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], = 0.04); : 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.
利伐沙班和达比加群常用于活动性癌症患者的血栓栓塞性疾病管理。然而，仅有有限的研究探讨了同步化疗对直接口服抗凝剂（DOAC）药效学的影响。我们研究的目的是评估利伐沙班和达比加群联合化疗对弥漫性大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，诊断为DLBCL且开始接受R-CHOP（利妥昔单抗、环磷酰胺、阿霉素、长春新碱和泼尼松）免疫化疗。入选的成年人接受利伐沙班（每日一次，每次10 mg）或达比加群酯（每日两次，每次110 mg）治疗。在R-CHOP给药前后的给药间隔内，评估服用利伐沙班的参与者的血浆抗Xa因子（FXa）和服用达比加群的参与者的稀释凝血酶时间（dTT）。利伐沙班和达比加群的药效学参数采用非房室分析确定。
26名成年人参与研究，利伐沙班组12人，达比加群组14人。平均年龄为59±14.4岁。在利伐沙班组，R-CHOP治疗后FXa抑制的曲线下效应浓度（AUEC）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治疗后dTT的AUEC保持不变（平均差异54.41 ng·h/mL，95% CI -99.09至207.9 ng/mL，P = 0.46）。然而，R-CHOP治疗后dTT达到峰值的中位时间明显加快（3小时，[最小值-最大值，1.5 - 8]），而未进行R-CHOP治疗时为（4小时，[最小值-最大值，3 - 8]，P = 0.04）。
同步R-CHOP化疗对利伐沙班抑制FXa或达比加群抑制dTT均无显著影响。达比加群与R-CHOP联合使用时，dTT达到峰值的时间更快。
