Haematology Department, Sir Charles Gairdner Hospital and Path West Laboratory Medicine, Hospital Avenue, Nedlands 6009, Western Australia.
Cancer Chemother Pharmacol. 2011 Apr;67(4):765-8. doi: 10.1007/s00280-010-1373-2. Epub 2010 Jun 8.
We report that hemodialysis clears Ara-U from the blood after high-dose Ara-C treatment in a patient with lymphoma and end-stage renal failure.
The patient received two doses of Ara-C 1 g/m(2) 24 h apart and was hemodialyzed at about 6 h after each dose and subsequently as per her usual dialysis schedule. Multiple blood samples were collected after dosing. Blood and dialyzate were also collected from the dialysis circuit during a second identical treatment cycle. Ara-C and its metabolite Ara-U in plasma and dialyzate were measured chromatographically, and the data subjected to pharmacokinetic analysis.
The distribution and elimination half-lives, steady-state volume of distribution and clearance values were 0.5 h, 7 h, 181 L and 307 l/h for Ara-C and 4.1 h, 34 h, 118 L and 2.64 l/h for Ara-U, respectively. The dialysis sessions immediately after the first and second doses cleared 39 and 52% (as Ara-U) of the respective Ara-C doses. Some 63% of Ara-U in plasma was extracted by dialysis. The patient showed no signs of neurotoxicity or other drug-related adverse effects.
Hemodialysis is very effective in clearing Ara-U from the plasma in renal failure, and this maneuver could easily be used routinely to prevent Ara-U accumulation and minimize adverse effects in patients with renal failure.
我们报告了一例淋巴瘤和终末期肾衰竭患者在高剂量阿糖胞苷(Ara-C)治疗后,通过血液透析清除阿糖胞苷(Ara-U)。
该患者接受了两次阿糖胞苷 1 g/m2,间隔 24 小时,在每次剂量后约 6 小时进行血液透析,并随后按照其常规透析计划进行。在给药后收集了多个血样。在第二个相同的治疗周期中,还从透析回路中收集了血液和透析液。通过色谱法测量了血浆和透析液中的阿糖胞苷及其代谢物阿糖脲嘧啶(Ara-U),并对数据进行了药代动力学分析。
阿糖胞苷和阿糖脲嘧啶的分布和消除半衰期、稳态分布容积和清除率分别为 0.5 h、7 h、181 L 和 307 l/h,4.1 h、34 h、118 L 和 2.64 l/h。第一次和第二次剂量后的透析立即清除了各自 Ara-C 剂量的 39%和 52%(以 Ara-U 计)。约 63%的阿糖脲嘧啶在血浆中被透析提取。该患者没有出现神经毒性或其他与药物相关的不良反应迹象。
血液透析在肾衰竭患者中非常有效地清除阿糖胞苷(Ara-U),这种操作可以很容易地常规用于预防阿糖胞苷(Ara-U)蓄积并最大限度地减少肾衰竭患者的不良反应。