Back to Search
Start Over
Characterization of the Effect of Renal Impairment on Upadacitinib Pharmacokinetics.
- Source :
-
Journal of clinical pharmacology [J Clin Pharmacol] 2019 Jun; Vol. 59 (6), pp. 856-862. Date of Electronic Publication: 2019 Jan 11. - Publication Year :
- 2019
-
Abstract
- Upadacitinib is a novel selective Janus kinase 1 inhibitor developed for treatment of rheumatoid arthritis and other autoimmune diseases. The objective of this study was to assess the pharmacokinetics and safety of a single upadacitinib dose in subjects with normal renal function and in subjects with renal impairment. A total of 24 subjects between the ages of 18 and 75 years were assigned to 1 of 4 renal function groups based on estimated glomerular filtration rate (normal, mild, moderate, severe; N = 6/group). A single 15-mg dose of upadacitinib extended-release formulation was administered under fasting conditions. Serial plasma and urine samples were assayed to evaluate the effect of renal impairment on upadacitinib exposure through regression analysis and analysis of covariance. The primary analysis was the regression analysis of upadacitinib exposures versus estimated glomerular filtration rate. The point estimates for upadacitinib plasma exposure ratios (90% confidence interval [CI]) in subjects with mild, moderate, and severe renal impairment were 1.18 (90%CI, 1.06-1.32), 1.33 (90%CI, 1.11-1.59), and 1.44 (90%CI, 1.14-1.82) for area under the plasma concentration-time curve and 1.06 (90%CI, 0.92-1.23), 1.11 (90%CI, 0.88-1.40), and 1.14 (90%CI, 0.84-1.56) for maximum observed plasma concentration, respectively, relative to subjects with normal renal function based on the regression analysis. The analysis of covariance categorical analysis provided consistent results. Upadacitinib was well tolerated by all subjects, and no safety issues were identified in subjects with renal impairment. Renal impairment has a limited effect on upadacitinib pharmacokinetics. This is in agreement with the known limited role of urinary excretion in upadacitinib elimination. Based on the limited impact on exposure, no dose adjustment is necessary for upadacitinib in subjects with impaired renal function.<br /> (© 2019, The Authors. The Journal of Clinical Pharmacology published by Wiley Periodicals, Inc. on behalf of American College of Clinical Pharmacology.)
- Subjects :
- Adolescent
Adult
Aged
Area Under Curve
Female
Glomerular Filtration Rate
Healthy Volunteers
Heterocyclic Compounds, 3-Ring blood
Heterocyclic Compounds, 3-Ring urine
Humans
Janus Kinase 1 antagonists & inhibitors
Janus Kinase Inhibitors blood
Janus Kinase Inhibitors urine
Male
Metabolic Clearance Rate drug effects
Middle Aged
Severity of Illness Index
Young Adult
Heterocyclic Compounds, 3-Ring pharmacokinetics
Heterocyclic Compounds, 3-Ring therapeutic use
Janus Kinase Inhibitors pharmacokinetics
Janus Kinase Inhibitors therapeutic use
Renal Insufficiency drug therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1552-4604
- Volume :
- 59
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Journal of clinical pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 30633369
- Full Text :
- https://doi.org/10.1002/jcph.1375