Department of Pharmacy, Okayama University Hospital.
Department of Medicinal Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences.
Acta Med Okayama. 2020 Dec;74(6):545-550. doi: 10.18926/AMO/61215.
Polymorphisms in methotrexate transporter pathways have been associated with methotrexate toxicities and clearance. Recent genome-wide association studies have revealed that the SLCO1B1 T521C variant is associated with methotrexate elimination. We present a case of a pediatric patient with acute lymphoblastic leukemia who suffered from persistently high plasma methotrexate concentrations and acute kidney injuries after the admin-istration of a medium dose of methotrexate. Subsequent genetic analysis showed that he was a carrier of dys-functional genetic variants associated with methotrexate clearance. This case highlights that polymorphisms of methotrexate transporter pathways can adversely affect methotrexate elimination in a clinically significant manner.
甲氨蝶呤转运途径的多态性与甲氨蝶呤的毒性和清除有关。最近的全基因组关联研究表明，SLCO1B1 T521C 变体与甲氨蝶呤的消除有关。我们报告了一例患有急性淋巴细胞白血病的儿科患者，在给予中等剂量的甲氨蝶呤后，他的血浆甲氨蝶呤浓度持续升高，并出现急性肾损伤。随后的基因分析显示，他是与甲氨蝶呤清除相关的功能异常遗传变异的携带者。本病例强调了甲氨蝶呤转运途径的多态性可能以临床显著的方式影响甲氨蝶呤的消除。
