AbbVie Inc., North Chicago, Illinois, USA.
Clin Pharmacol Drug Dev. 2021 Mar;10(3):299-306. doi: 10.1002/cpdd.844. Epub 2020 Jul 9.
This phase 1 study characterized the effect of multiple doses of upadacitinib, an oral Janus kinase 1 selective inhibitor, on the pharmacokinetics of the cytochrome P450 (CYP) 2B6 substrate bupropion. Healthy subjects (n = 22) received a single oral dose of bupropion 150 mg alone (study period 1) and on day 12 of a 16-day regimen of upadacitinib 30 mg once daily (study period 2). Serial blood samples for measurement of bupropion and hydroxybupropion plasma concentrations were collected in each study period. The central values (90% confidence intervals) for the ratios of change were 0.87 (0.79-0.96) for bupropion maximum plasma concentration (C ), 0.92 (0.87-0.98) for bupropion area under the plasma-concentration time curve from time 0 to infinity (AUC ), 0.78 (0.72-0.85) for hydroxybupropion C , and 0.72 (0.67-0.78) for hydroxybupropion AUC when administered with, relative to when administered without, upadacitinib. After multiple-dose administration of upadacitinib 30 mg once daily, upadacitinib mean ± SD AUC was 641 ± 177 ng·h/mL, and C was 83.3 ± 30.7 ng/mL. These results confirm that upadacitinib has no relevant effect on pharmacokinetics of substrates metabolized by CYP2B6.
这项 1 期研究描述了口服 Janus 激酶 1 选择性抑制剂 upadacitinib 多次给药对细胞色素 P450（CYP）2B6 底物安非他酮药代动力学的影响。健康受试者（n=22）单独接受单次口服安非他酮 150 mg（研究期 1）和 upadacitinib 16 天疗程的第 12 天，每天口服 30 mg（研究期 2）。在每个研究期间采集用于测量安非他酮和羟基安非他酮血浆浓度的连续血样。变化比值的中心值（90%置信区间）分别为安非他酮最大血浆浓度（C ）的 0.87（0.79-0.96）、安非他酮从 0 到无穷时的血浆浓度-时间曲线下面积（AUC ）的 0.92（0.87-0.98）、羟基安非他酮 C 的 0.78（0.72-0.85）和羟基安非他酮 AUC 的 0.72（0.67-0.78），当与 upadacitinib 联合给药时与单独给药时相比。在每天口服 upadacitinib 30 mg 多次给药后，upadacitinib 的平均±SD AUC 为 641±177ng·h/mL，C 为 83.3±30.7ng/mL。这些结果证实，upadacitinib 对 CYP2B6 代谢的底物的药代动力学没有相关影响。
