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 (Cmax ), 0.92 (0.87-0.98) for bupropion 
area under the plasma-concentration time curve from time 0 to infinity (AUCinf 
), 0.78 (0.72-0.85) for hydroxybupropion Cmax , and 0.72 (0.67-0.78) for 
hydroxybupropion AUCinf when administered with, relative to when administered 
without, upadacitinib. After multiple-dose administration of upadacitinib 30 mg 
once daily, upadacitinib mean ± SD AUC0-24 was 641 ± 177 ng·h/mL, and Cmax was 
83.3 ± 30.7 ng/mL. These results confirm that upadacitinib has no relevant 
effect on pharmacokinetics of substrates metabolized by CYP2B6.