Department of Pharmacy Practice, University of Illinois at Chicago College of Pharmacy, Chicago, Illinois; University of Cincinnati Health, Department of Pharmacy Services, Cincinnati, Ohio.
Department of Pharmacy Practice, University of Illinois at Chicago College of Pharmacy, Chicago, Illinois.
Int J Antimicrob Agents. 2023 Sep;62(3):106920. doi: 10.1016/j.ijantimicag.2023.106920. Epub 2023 Jul 11.
To date, there are no published pharmacokinetic (PK) data for baricitinib in critically ill patients requiring continuous renal replacement therapy. This paper describes in detail the plasma PK and dialytic clearance of baricitinib in a patient infected with coronavirus disease 2019 (COVID-19) requiring continuous renal replacement therapy in order to suggest dosing strategies in this population.
Baricitinib 2 mg daily was used for the treatment of COVID-19 in a critically ill patient on continuous venovenous haemodialysis (CVVHD). Prefiltration plasma drug concentrations of baricitinib were measured at hours 1, 2, 12, and 24 after drug administration. Postfiltration and ultrafiltrate concentrations were collected at hour 24.
Plasma PK parameters of baricitinib in this patient were as follows: maximum plasma concentration (C), 20.98 ng/mL; minimum plasma concentration (C), 9.84 ng/mL; half-life (t), 23.85 h; apparent volume of distribution at the steady state (V), 99.42 L; total clearance at the steady state (CL), 2.89 L/h; and area under the concentration-time curve (AUC), 692.14 ng · h/mL. The saturation coefficient for baricitinib at 24 h after administration was 0.607. The transmembrane clearance of baricitinib by CVVHD running at a flow rate of 2 L/h was 1.21 L/h, representing 41.9% of the total clearance of baricitinib.
In a critically ill COVID-19 patient on CVVHD, a 2-mg dose of baricitinib achieves a C comparable with healthy subjects, but total clearance was reduced to about 20%. Larger studies exploring multiple patients and dialysis modes are needed to determine the optimal dosing strategy for baricitinib in this patient population.
迄今为止，尚无巴瑞替尼在需要连续肾脏替代治疗的重症 COVID-19 患者中的药代动力学（PK）数据。本文详细描述了 1 例 COVID-19 重症患者在接受连续静脉-静脉血液透析（CVVHD）治疗时的巴瑞替尼血浆 PK 和透析清除率，以提出该人群的给药策略。
1 例 COVID-19 重症患者接受 CVVHD 治疗，每日给予巴瑞替尼 2mg。给药后 1、2、12 和 24 小时测量巴瑞替尼预滤过血浆药物浓度。在 24 小时收集后滤过液和超滤液浓度。
该患者巴瑞替尼的血浆 PK 参数如下：最大血浆浓度（C）为 20.98ng/ml；最小血浆浓度（C）为 9.84ng/ml；半衰期（t）为 23.85h；稳态表观分布容积（V）为 99.42L；稳态总清除率（CL）为 2.89L/h；浓度-时间曲线下面积（AUC）为 692.14ng·h/ml。给药 24 小时后，巴瑞替尼的饱和度系数为 0.607。以 2L/h 的流速运行的 CVVHD 对巴瑞替尼的跨膜清除率为 1.21L/h，占巴瑞替尼总清除率的 41.9%。
在接受 CVVHD 的 COVID-19 重症患者中，2mg 剂量的巴瑞替尼可达到与健康受试者相当的 C，但总清除率降低至约 20%。需要更大规模的研究来探索多种患者和透析模式，以确定该人群中巴瑞替尼的最佳给药策略。
