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

British Journal of Clinical Pharmacology
Mohamed-Eslam F MohamedAhmed A Othman

Abstract

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 on upadacitinib pharmacokinetics. Two Phase 1 evaluations were conducted, each in 12 healthy subjects. In Study 1, using a randomized, two-sequence crossover design, a 3 mg dose of upadacitinib (immediate-release capsules) was administered alone under fasting conditions, after high-fat meal, or on Day 4 of a 6-day regimen of 400 mg once-daily ketoconazole. In Study 2, a 12 mg upadacitinib dose was administered alone, with the first, and with the eighth dose of a 9-day regimen of rifampin 600 mg once daily. Upadacitinib plasma concentrations were characterized. Administration of upadacitinib immediate-release capsules after a high-fat meal decreased upadacitinib Cmax by 23% and had no impact on upadacitinib AUC relative to the fasting conditions. Ketoconazole (strong CYP3A inhibitor) increased upadacitinib Cmax and AUC by 70% and 75%, respectively. Multiple doses of rifampin (broad CYP inducer) decreased upadacitinib Cmax and AUC by approxi...Continue Reading

References

Jun 20, 2003·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Thorir D BjornssonUNKNOWN FDA Center for Drug Evaluation and Research (CDER)
Jul 29, 2003·Clinical Pharmacokinetics·Mikko NiemiKari T Kivistö
Sep 13, 2005·Clinical Pharmacology and Therapeutics·Richard H Ho, Richard B Kim
Sep 30, 2009·British Journal of Pharmacology·A Kalliokoski, M Niemi
Apr 22, 2014·Clinical Pharmacology and Therapeutics·A B KeS D Hall
May 14, 2014·Expert Opinion on Investigational Drugs·Peter Norman
Jun 6, 2015·Journal of Clinical Pharmacology·Lichuan LiuSarah M Robertson
Dec 10, 2015·British Journal of Pharmacology·Stephen Ph AlexanderCgtp Collaborators
Dec 10, 2015·British Journal of Pharmacology·Stephen Ph AlexanderUNKNOWN CGTP Collaborators

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Citations

Mar 6, 2018·Basic & Clinical Pharmacology & Toxicology·Falko PartoschUrsula Gundert-Remy
Jun 26, 2018·Expert Opinion on Investigational Drugs·Ferdinando D'AmicoSilvio Danese
Jan 12, 2019·Journal of Clinical Pharmacology·Mohamed-Eslam F MohamedAhmed A Othman
Apr 12, 2019·Journal of Clinical Pharmacology·Sheryl TruemanAhmed A Othman
Apr 6, 2019·Current Pharmaceutical Design·Agnès Fernández-ClotetJulián Panés
Mar 12, 2020·Journal of Crohn's & Colitis·Pavine L C Lefevre, Niels Vande Casteele
Jun 11, 2020·Expert Review of Gastroenterology & Hepatology·Giulia RodaSilvio Danese
Jul 11, 2020·Clinical Pharmacology in Drug Development·Mohamed-Eslam F MohamedAhmed A Othman
May 6, 2020·Drug Safety : an International Journal of Medical Toxicology and Drug Experience·Vijayabhaskar VeeravalliNuggehally R Srinivas
Oct 24, 2019·Drugs·Sean Duggan, Susan J Keam
Dec 24, 2019·Clinical Pharmacokinetics·Mohamed-Eslam F MohamedAhmed A Othman
Jun 11, 2021·Clinical Pharmacology in Drug Development·Mohamed-Eslam F MohamedAhmed A Othman
Sep 4, 2021·The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation·Maria M CrespoAllan R Glanville

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