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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. [ABSTRACT FROM AUTHOR]

Upadacitinib is a novel selective oral Janus kinase 1 (JAK) inhibitor being developed for treatment of several inflammatory diseases. Oral contraceptives are anticipated to be a common concomitant medication in the target patient populations. This study was designed to evaluate the effect of multiple doses of upadacitinib on the pharmacokinetics of ethinylestradiol and levonorgestrel in healthy female subjects. This phase I, single‐center, open‐label, 2‐period crossover study evaluated the effect of multiple doses of 30 mg once daily extended‐release upadacitinib on the pharmacokinetics of a single oral dose of ethinylestradiol/levonorgestrel (0.03/0.15 mg; administered alone in period 1 and on day 12 of a 14‐day regimen of upadacitinib in period 2) in 22 healthy female subjects. The ratios (90% confidence intervals) for maximum plasma concentration and area under the plasma drug concentration–time curve from time zero to infinity following administration of ethinylestradiol/levonorgestrel with upadacitinib compared with administration of ethinylestradiol/ levonorgestrel alone were 0.96 (0.89–1.02) and 1.1 (1.04–1.19), respectively, for ethinylestradiol, and 0.96 (0.87–1.06) and 0.96 (0.85–1.07), respectively, for levonorgestrel. The harmonic mean terminal half‐life for ethinylestradiol (7.7 vs 7.0 hours) and levonorgestrel (37.1 vs 33.1 hours) was similar in the presence and absence of upadacitinib. Ethinylestradiol and levonorgestrel were bioequivalent in the presence and absence of upadacitinib. Therefore, upadacitinib can be administered concomitantly with oral contraceptives containing ethinylestradiol or levonorgestrel. [ABSTRACT FROM AUTHOR]