Department of Medical Sciences, Infectious Diseases, University of Turin, Italy.
Tufts School of Medicine, Boston, MA, USA.
Br J Clin Pharmacol. 2021 Dec;87(12):4861-4867. doi: 10.1111/bcp.14895. Epub 2021 Jul 4.
Remdesivir is one of the most encouraging treatments against SARS-CoV-2 infection. After intravenous infusion, RDV is rapidly metabolized (t = 1 h) within the cells to its active adenosine triphosphate analogue form (GS-443902) and then it can be found in plasma in its nucleoside analogue form (GS-441524). In this real-life study, we describe the remdesivir and GS-441524 concentrations at three time points in nine ICU patients, through a validated ultra-high-performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) method. The observed data confirmed the very rapid conversion of RDV to its metabolite and the quite long half-life of GS-441524. The mean C , C and AUC , were < 0.24 ng/mL and 122.3 ng/mL, 2637.3 ng/mL and 157.8 ng/mL, and 5171.2 ngh/mL and 3676.5 ng*h/ml, respectively, for RDV and GS-441524. Three out of nine patients achieved a C > 2610 ng/mL and 140 ng/mL and AUC > 1560 ngh/mL and 2230 ng*h/mL for RDV and GS-441524, respectively. The mean t value for GS-441524 was 26.3 h. Despite the low number of patients, these data can represent an interesting preliminary report on the variability of RDV and GS-441524 concentrations in a real-life ICU setting.
瑞德西韦是治疗 SARS-CoV-2 感染最有希望的药物之一。静脉输注后,RDV 在细胞内迅速代谢(t = 1 小时)为其活性三磷酸腺苷类似物形式(GS-443902),然后可以在血浆中以核苷类似物形式(GS-441524)发现。在这项真实世界的研究中,我们通过经过验证的超高效液相色谱串联质谱(UHPLC-MS/MS)方法,描述了 9 例 ICU 患者在三个时间点的瑞德西韦和 GS-441524 浓度。观察到的数据证实了 RDV 非常迅速地转化为其代谢物,以及 GS-441524 相当长的半衰期。RDV 和 GS-441524 的平均 C 、 C 和 AUC 分别为 <0.24ng/mL 和 122.3ng/mL、2637.3ng/mL 和 157.8ng/mL、5171.2ngh/mL 和 3676.5ng*h/ml。9 例患者中有 3 例达到了 RDV 的 C > 2610ng/mL 和 140ng/mL,以及 AUC > 1560ngh/mL 和 2230ng*h/mL;GS-441524 的平均 t 值为 26.3 小时。尽管患者数量较少,但这些数据可以代表在真实 ICU 环境中瑞德西韦和 GS-441524 浓度变异性的一个有趣的初步报告。