Department of Pharmacy, Beijing Tiantan Hospital, Capital Medical University, Beijing, P. R. China.
Department of Clinical Pharmacology, College of Pharmaceutical Sciences, Capital Medical University, Beijing, P. R. China.
Expert Opin Drug Metab Toxicol. 2024 Apr;20(4):263-274. doi: 10.1080/17425255.2024.2332366. Epub 2024 Mar 19.
High-dose methotrexate (HDMTX) therapy poses challenges in various neoplasms due to individualized pharmacokinetics and associated adverse effects. Our purpose is to identify early risk factors associated with HDMTX-induced toxicities, paving the way for personalized treatment.
A systematic review of PubMed and Cochrane databases was conducted for articles from inception to July 2023. Eligible studies included reviews, clinical trials, and real-world analyses. Irrelevant studies were excluded, and manual searches and citation reviews were performed. Factors such as MTX exposure, drug interactions, demographics, serum albumin, urine pH, serum calcium, and genetic polymorphisms affecting MTX transport (e.g. SLCO1B1), intracellular folate metabolism (MTHFR), cell development (ARID5B), metabolic pathways (UGT1A1, PNPLA3), as well as epigenetics were identified.
This comprehensive review aids researchers and clinicians in early identification of HDMTX toxicity risk factors. By understanding the multifaceted risk factors associated with hematologic malignancies, personalized treatment approaches can be tailored to optimize therapeutic outcomes.
高剂量甲氨蝶呤（HDMTX）治疗由于个体药代动力学和相关不良反应，在各种肿瘤中带来挑战。我们的目的是确定与 HDMTX 诱导的毒性相关的早期风险因素，为个性化治疗铺平道路。
对从建立到 2023 年 7 月的 PubMed 和 Cochrane 数据库进行了系统回顾。合格的研究包括综述、临床试验和真实世界分析。排除不相关的研究，并进行手动搜索和引文审查。确定了影响 MTX 转运（如 SLCO1B1）、细胞内叶酸代谢（MTHFR）、细胞发育（ARID5B）、代谢途径（UGT1A1、PNPLA3）以及表观遗传学的 MTX 暴露、药物相互作用、人口统计学、血清白蛋白、尿液 pH 值、血清钙和遗传多态性等因素。
这项全面的综述有助于研究人员和临床医生早期识别 HDMTX 毒性的风险因素。通过了解与血液系统恶性肿瘤相关的多方面风险因素，可以制定个性化的治疗方法，以优化治疗结果。
