Department of Intensive Care, Cliniques universitaires Saint-Luc, Brussels, Belgium.
Univ Rennes, CHU Rennes, Inserm, EHESP, Irset (Institut de recherche en santé, environnement et travail)-UMR_S 1085, Rennes, France.
Br J Clin Pharmacol. 2023 May;89(5):1686-1689. doi: 10.1111/bcp.15686. Epub 2023 Feb 19.
A 53-year-old woman with a history of acute myeloid leukaemia received a second allogeneic haematopoietic stem cell transplant and was prescribed, among other medications, acyclovir and letermovir (480-mg daily oral dose) for prophylaxis of, respectively, herpes simplex and cytomegalovirus infection. The patient was admitted in the intensive care unit for dyspnoea and oliguria. Laboratory investigations revealed acute kidney injury but also a severe and progressive lactic acidosis. Liver function tests were within normal range. The combination of lactic acidosis, hypoglycaemia and acylcarnitine profile in plasma raised the suspicion of mitochondrial toxicity. Letermovir therapy was interrupted, and determination of plasma letermovir pharmacokinetics revealed a prolonged terminal half-life (38.7 h) that was not significantly influenced by continuous venovenous haemofiltration. Exploration for genetic polymorphisms revealed that the patient was SLCO1B1*5/*15 (c.521T>C homozygous carrier and c.388A>G heterozygous carrier) with a predicted nonfunctional organic anion transporting polypeptide 1B1 protein. The relationship between letermovir accumulation and development of lactic acidosis requires further observations.
一位 53 岁女性，有急性髓系白血病病史，接受了第二次同种异体造血干细胞移植，并接受了阿昔洛韦和乐韦（每日口服 480 毫克剂量）等药物预防单纯疱疹和巨细胞病毒感染。患者因呼吸困难和少尿而住进重症监护病房。实验室检查显示急性肾损伤，但也存在严重且进行性的乳酸酸中毒。肝功能检查在正常范围内。乳酸酸中毒、低血糖和血浆酰基肉碱谱的结合提示线粒体毒性。乐韦治疗被中断，乐韦的药代动力学检测结果显示终末半衰期延长（38.7 小时），但连续静脉-静脉血液滤过对其无明显影响。对遗传多态性的探索表明，该患者是 SLCO1B1*5/*15（c.521T>C 纯合子携带者和 c.388A>G 杂合子携带者），预测有机阴离子转运多肽 1B1 蛋白无功能。乐韦蓄积与乳酸酸中毒发展之间的关系需要进一步观察。
