Assessment of effect of CYP3A inhibition, CYP induction, OATP1B inhibition, and high‐fat meal on pharmacokinetics of the JAK1 inhibitor upadacitinib

• Published in: British journal of clinical pharmacology Vol. 83; no. 10; pp. 2242 - 2248
• Main Authors: Mohamed, Mohamed‐Eslam F., Jungerwirth, Steven, Asatryan, Armen, Jiang, Ping, Othman, Ahmed A.
• Format: Journal Article
• Language: English
• Published: England John Wiley and Sons Inc 01.10.2017
• Subjects: Adult; Area Under Curve; Autoimmune Diseases - drug therapy; Cross-Over Studies; Cytochrome P-450 CYP3A - metabolism; Cytochrome P-450 CYP3A Inducers - pharmacokinetics; Cytochrome P-450 CYP3A Inhibitors - pharmacokinetics; Diet, High-Fat; Dietary Fats - pharmacokinetics; Drug Interactions; Fasting; Female; Food-Drug Interactions; Healthy Volunteers; Heterocyclic Compounds, 3-Ring - pharmacology; Heterocyclic Compounds, 3-Ring - therapeutic use; high‐fat meal; Humans; JAK1 inhibitor; Janus Kinase 1 - antagonists & inhibitors; ketoconazole; Ketoconazole - pharmacokinetics; Liver-Specific Organic Anion Transporter 1 - antagonists & inhibitors; Male; Middle Aged; pharmacokinetics; Protein Kinase Inhibitors - pharmacology; rifampin; Rifampin - pharmacokinetics; upadacitinib; Young Adult; high-fat meal; upadacitinib; pharmacokinetics; JAK1 inhibitor; ketoconazole; rifampin

Aims Upadacitinib (ABT‐494) is a selective Janus kinase 1 inhibitor being developed for treatment of auto‐immune inflammatory disorders. This work evaluated effects of high‐fat meal, cytochrome P450 (CYP) 3A inhibition, CYP induction, and organic anion transporting polypeptide (OATP) 1B inhibition o...