BACKGROUND Limited data exist for dosing of zanamivir in the setting of CVVH in the intensive care unit (ICU). Our objective is to report the pharmacokinetics and sieving coefficient (Sv) of zanamivir in patients receiving continuous venovenous hemofiltration (CVVH). METHODS In this prospective observational study, patients of ≥18 years admitted to the ICU with a life-threatening Influenza A or B infection, treated with zanamivir i.v. undergoing CVVH were included. Patients received a zanamivir loading dose of 600 mg i.v., 12 h later followed by maintenance dosages two times daily according to the treating physician. Per patient, nine CFT plasma and nine ultrafiltrate samples were drawn on day 2 of treatment and analysed with a validated HPLC-MS/MS method. RESULTS Four patients were included in the study. The zanamivir elimination half-life was prolonged with 5.6-9.9 h, compared to patients with normal renal function. A Sv of approximately 1.0 was identified, with unrestricted transport of zanamivir to the ultrafiltrate. CONCLUSIONS Zanamivir is well cleared by CVVH. In absence of the possibility for therapeutic drug monitoring, the ultrafiltration rate seems as a good surrogate parameter to estimate the CLCVVH and may help guide the dosing of zanamivir.

中文翻译：

---

扎那米韦在接受连续静脉血液滤过的危重患者中的药代动力学。

背景 在重症监护病房 (ICU) 中存在 CVVH 情况下扎那米韦给药的数据有限。我们的目标是报告扎那米韦在接受连续静脉血液滤过 (CVVH) 治疗的患者中的药代动力学和筛分系数 (Sv)。方法 在这项前瞻性观察性研究中，纳入了 ≥ 18 岁并因危及生命的甲型或乙型流感感染而入住 ICU、接受扎那米韦静脉注射治疗并接受 CVVH 治疗的患者。根据主治医师的说法，患者接受 600 mg 静脉注射扎那米韦负荷剂量，12 小时后每天两次维持剂量。每位患者在治疗的第 2 天抽取 9 个 CFT 血浆和 9 个超滤液样本，并使用经过验证的 HPLC-MS/MS 方法进行分析。结果 4 名患者被纳入研究。与肾功能正常的患者相比，扎那米韦的消除半衰期延长了 5.6-9.9 小时。确定了大约 1.0 的 Sv，扎那米韦不受限制地转运至超滤液。结论 CVVH 可以很好地清除扎那米韦。在无法进行治疗药物监测的情况下，超滤率似乎是估计 CLCVVH 的一个很好的替代参数，可能有助于指导扎那米韦的剂量。