Xu Qinxia, Li Ziran, Ding Tianling, Qiu Xiaoyan, Wu Zhuo
Department of Pharmacy, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, China.
Department of Pharmacy, Huashan Hospital, Fudan University, 12 Middle Urumqi Road, Shanghai, 200040, China.
Ann Hematol. 2025 Jan;104(1):457-465. doi: 10.1007/s00277-024-06146-4. Epub 2024 Dec 18.
This retrospective study investigated the potential drug-drug interactions between trimethoprim-sulfamethoxazole (TMP-SMZ) and high-dose methotrexate (HD-MTX) in adult patients with primary central nervous system lymphoma (PCNSL). A total of 143 Chinese adult patients with PCNSL who received 498 cycles of MTX were included. Differences in the pharmacokinetics of MTX, including C, clearance (CL) and AUC with and without co-administration of TMP-SMZ were assessed. The incidence of MTX-related acute kidney injury (AKI), hepatotoxicity, myelosuppression, and delayed MTX elimination at 48 and 72 h were also compared. Patients were divided into two cohorts for analysis: 146 cycles with TMP-SMZ exposure and 352 cycles without TMP-SMZ exposure. Patients who received TMP-SMZ concurrently with HD-MTX exhibited a 1.13-fold increase in C, a 1.12-fold increase in AUC and a reduction in CL by 0.87-fold for MTX. There was no significant difference in the incidence of MTX-related AKI, hepatotoxicity, myelosuppression, or delayed MTX elimination between the two cohorts. Prophylactic TMP-SMZ might lead to increased MTX exposure but has no impact on the incidence of myelosuppression, AKI, and hepatotoxicity. These results suggested that prophylactic TMP-SMZ is safe for adult patients with PCNSL receiving HD-MTX.
这项回顾性研究调查了复方磺胺甲恶唑（TMP-SMZ）与高剂量甲氨蝶呤（HD-MTX）在原发性中枢神经系统淋巴瘤（PCNSL）成年患者中的潜在药物相互作用。共纳入143例接受了498个周期甲氨蝶呤治疗的中国成年PCNSL患者。评估了联合使用与未联合使用TMP-SMZ时甲氨蝶呤的药代动力学差异，包括血药浓度（C）、清除率（CL）和曲线下面积（AUC）。还比较了甲氨蝶呤相关急性肾损伤（AKI）、肝毒性、骨髓抑制以及48小时和72小时时甲氨蝶呤清除延迟的发生率。患者被分为两个队列进行分析：146个周期有TMP-SMZ暴露，352个周期无TMP-SMZ暴露。同时接受TMP-SMZ和HD-MTX的患者，其甲氨蝶呤的C增加1.13倍，AUC增加1.12倍，CL降低0.87倍。两个队列之间甲氨蝶呤相关的AKI、肝毒性、骨髓抑制或甲氨蝶呤清除延迟的发生率没有显著差异。预防性使用TMP-SMZ可能会导致甲氨蝶呤暴露增加，但对骨髓抑制、AKI和肝毒性的发生率没有影响。这些结果表明，预防性使用TMP-SMZ对接受HD-MTX治疗的成年PCNSL患者是安全的。
