Mertens Beatrijs, Elkayal Omar, Dreesen Erwin, Wauters Joost, Meersseman Philippe, Debaveye Yves, Degezelle Karlien, Vermeersch Pieter, Gijsen Matthias, Spriet Isabel
Department of Pharmaceutical and Pharmacological Sciences, KU Leuven and Pharmacy Department, University Hospitals Leuven, 3000 Leuven, Belgium.
Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, 3000 Leuven, Belgium.
Antibiotics (Basel). 2023 Jun 21;12(7):1085. doi: 10.3390/antibiotics12071085.
Effective dosing of isavuconazole in patients supported by extracorporeal membrane oxygenation (ECMO) is important due to the role of isavuconazole as a first-line treatment in patients with influenza- and COVID-19-associated pulmonary aspergillosis. To date, robust pharmacokinetic data in patients supported by ECMO are limited. Therefore, it is unknown whether ECMO independently impacts isavuconazole exposure. We measured isavuconazole plasma concentrations in two patients supported by ECMO and estimated individual pharmacokinetic parameters using non-compartmental analysis and two previously published population pharmacokinetic models. Furthermore, a narrative literature review on isavuconazole exposure in adult patients receiving ECMO was performed. The 24 h areas under the concentration-time curve and trough concentrations of isavuconazole were lower in both patients compared with exposure values published before. In the literature, highly variable isavuconazole concentrations have been documented in patients with ECMO support. The independent effect of ECMO versus critical illness itself on isavuconazole exposure cannot be deduced from our and previously published (case) reports. Pending additional data, therapeutic drug monitoring is recommended in critically ill patients, regardless of ECMO support.
由于异氟康唑在流感和新冠病毒相关肺曲霉病患者的一线治疗中发挥作用，因此在接受体外膜肺氧合（ECMO）支持的患者中确定异氟康唑的有效剂量非常重要。迄今为止，关于接受ECMO支持患者的可靠药代动力学数据有限。因此，尚不清楚ECMO是否会独立影响异氟康唑的血药浓度。我们测定了两名接受ECMO支持患者的异氟康唑血浆浓度，并使用非房室分析和两个先前发表的群体药代动力学模型估算了个体药代动力学参数。此外，我们还对接受ECMO的成年患者的异氟康唑血药浓度进行了叙述性文献综述。与之前公布的暴露值相比，两名患者的异氟康唑24小时浓度-时间曲线下面积和谷浓度均较低。在文献中，已记录到接受ECMO支持的患者异氟康唑浓度变化很大。从我们的报告和之前发表的（病例）报告中无法推断出ECMO与危重病本身对异氟康唑暴露的独立影响。在获得更多数据之前，建议对危重症患者进行治疗药物监测，无论其是否接受ECMO支持。
