Department of Pharmaceutical and Pharmacological Sciences, KU Leuven and Pharmacy Department, University Hospitals Leuven, Leuven, Belgium.
Department of Pharmacy and Radboud Institute for Health Sciences, Radboud University Medical Center, Nijmegen and Center of Expertise in Mycology Radboudumc/CWZ, Radboud University Medical Center, Nijmegen, The Netherlands.
J Antimicrob Chemother. 2021 Apr 13;76(5):1234-1241. doi: 10.1093/jac/dkab012.
Posaconazole is an antifungal drug used for prophylaxis and treatment of invasive fungal infections. Severe influenza has been identified as a risk factor for invasive pulmonary aspergillosis in critically ill patients. In this population, extracorporeal membrane oxygenation (ECMO) is used as rescue therapy, although little is known about the pharmacokinetics (PK) of posaconazole during ECMO.
To determine the PK and target attainment of six patients treated with IV posaconazole under ECMO and to develop a population PK model that can be used to simulate the PTA.
Critically ill patients treated with posaconazole and ECMO were included in this study. Plasma samples were collected at several timepoints within one dosing interval on two occasions: an early (Day 2-3) and a late (Day 4-7) sampling day. Daily trough concentrations were measured.
The median (IQR) AUC0-24, CL and Vd were 34.3 (28.3-37.7) mg·h/L, 8.7 (8.0-10.6) L/h and 389 (314-740) L, if calculated with non-compartmental analysis based on the observed concentrations. All measured trough concentrations were ≥0.7 mg/L and 11/16 were ≥1 mg/L, which are the haematological thresholds for prophylaxis and treatment of invasive aspergillosis, respectively. The targeted PTA (>90%) was attained for prophylaxis but not for treatment.
ECMO does not appear to influence posaconazole exposure compared with haematology patients. However, some trough levels were below the lower limit for treatment. An a priori dose adjustment does not appear to be necessary but drug monitoring is recommended.
泊沙康唑是一种抗真菌药物，用于预防和治疗侵袭性真菌感染。严重流感已被确定为危重症患者侵袭性肺曲霉病的危险因素。在这种人群中，体外膜肺氧合（ECMO）被用作挽救性治疗，尽管关于 ECMO 期间泊沙康唑的药代动力学（PK）知之甚少。
确定六名接受 ECMO 下 IV 泊沙康唑治疗的患者的 PK 和目标获得情况，并开发一个可用于模拟 PTA 的群体 PK 模型。
本研究纳入了接受泊沙康唑和 ECMO 治疗的危重症患者。在两次情况下，在一个给药间隔内的几个时间点采集血浆样本：早期（第 2-3 天）和晚期（第 4-7 天）采样日。每天测量谷浓度。
基于观察浓度的非房室分析，中位（IQR）AUC0-24、CL 和 Vd 分别为 34.3（28.3-37.7）mg·h/L、8.7（8.0-10.6）L/h 和 389（314-740）L。所有测量的谷浓度均≥0.7mg/L，11/16 均≥1mg/L，分别为预防和治疗侵袭性曲霉病的血液学阈值。预防的目标 PTA（>90%）达到，但治疗的未达到。
与血液科患者相比，ECMO 似乎不会影响泊沙康唑的暴露。然而，一些谷浓度低于治疗的下限。似乎不需要预先调整剂量，但建议进行药物监测。
