Service de Réanimation, CH de St BRIEUC, 10, rue Marcel Proust, 22000 Saint-Brieuc, France.
Laboratoire de Pharmacologie, CHU de Rennes, 2, rue Henri le Guilloux, 35000 Rennes, France.
Clin Biochem. 2023 Aug;118:110601. doi: 10.1016/j.clinbiochem.2023.110601. Epub 2023 Jun 22.
The use of the selective Janus Kinase 1/2 inhibitor baricitinib has shown a survival benefit in mechanically ventilated COVID-19 patients but this is not without adverse drug reactions. Although critically ill patients are at risk of altered drug exposure, data on baricitinib pharmacokinetics (PK) are scarce. This study describes real-life baricitinib plasma exposure in critically ill COVID-19 patients.
This retrospective observational study was conducted in critically ill patients with COVID-19 treated with baricitinib 4 mg/day. Plasma concentrations were measured at predose (C0), 1 h (C1) and 3 h (C3) after the drug intake. PK and area under the curve (AUC) were estimated using non-compartmental pharmacokinetic analysis.
Seven patients contributed to 22 baricitinib plasma concentration measurements after a median [range] of 3 days [2-3] of treatment. Median baricitinib plasma concentrations were 2.2 ng/mL [1.4-8.0], 24.0 ng/mL [4.9-37.3] and 14.1 ng/mL [8.3-15.1] for trough (C0), C1 and C3 concentrations respectively. The median AUC 0-24 h was 188.8 ng.h/mL [141.3-236.3]. No difference was observed in C0 and C1 when comparing patients according to body mass index < or > 30. The patient with the lowest glomerular filtration rate (74 mL/min) had the highest baricitinib trough concentration. Overall, 2 patients had liver function test perturbation and both of them had atypical PK with delayed time to reach maximum concentration.
High inter-patient variability and relatively low baricitinib trough concentrations and AUC were observed in critically ill COVID-19 patients receiving the usual dosage of 4 mg/day. This preliminary study encourages further exploration of the concentration-effect relationship of baricitinib in this clinical context.
选择性 Janus 激酶 1/2 抑制剂巴瑞替尼的使用在接受机械通气的 COVID-19 患者中显示出了生存获益，但这并非没有药物不良反应。虽然危重症患者存在药物暴露改变的风险，但有关巴瑞替尼药代动力学（PK）的数据却很少。本研究描述了在 COVID-19 危重症患者中真实的巴瑞替尼血浆暴露情况。
这是一项回顾性观察性研究，纳入了接受巴瑞替尼 4mg/天治疗的 COVID-19 危重症患者。在给药前（C0）、给药后 1 小时（C1）和 3 小时（C3）时测量血浆浓度。采用非房室 PK 分析估算 PK 参数和药时曲线下面积（AUC）。
7 例患者在接受治疗 3 天[2-3]后共提供了 22 次巴瑞替尼血浆浓度测量值。谷值（C0）、C1 和 C3 浓度的中位巴瑞替尼血浆浓度分别为 2.2ng/mL[1.4-8.0]、24.0ng/mL[4.9-37.3]和 14.1ng/mL[8.3-15.1]。0-24 小时 AUC 中位值为 188.8ng·h/mL[141.3-236.3]。根据体重指数<30 或>30 将患者进行比较时，C0 和 C1 浓度没有差异。肾小球滤过率最低的患者（74mL/min）的巴瑞替尼谷浓度最高。总的来说，有 2 例患者的肝功能检测出现异常，且这 2 例患者均存在 PK 异常，表现为达到最大浓度的时间延迟。
在接受 4mg/天常规剂量的 COVID-19 危重症患者中，观察到巴瑞替尼的个体间变异性高，且巴瑞替尼的谷浓度和 AUC 相对较低。这项初步研究鼓励进一步探索巴瑞替尼在这种临床情况下的浓度-效应关系。
