Pharmacokinetics of Upadacitinib in Healthy Subjects and Subjects With Rheumatoid Arthritis, Crohn's Disease, Ulcerative Colitis, or Atopic Dermatitis: Population Analyses of Phase 1 and 2 Clinical Trials.

Pharmacokinetics of Upadacitinib in Healthy Subjects and Subjects With Rheumatoid Arthritis, Crohn's Disease, Ulcerative Colitis, or Atopic Dermatitis: Population Analyses of Phase 1 and 2 Clinical Trials. J Clin Pharmacol. 2019 Nov 07;: Authors: Nader A, Stodtmann S, Friedel A, Mohamed MF, Othman AA Abstract Upadacitinib (ABT-494) is a selective Janus kinase (JAK)1 inhibitor being developed for treatment of several inflammatory disorders. A population pharmacokinetic model was developed for upadacitinib using 11,658 plasma concentrations from 1145 subjects from 4 phase 1 and 5 phase 2 studies in healthy subjects and subjects with rheumatoid arthritis, Crohn's disease, ulcerative colitis, or atopic dermatitis. A 2-compartment model with first-order absorption and lag time for the immediate-release formulation and mixed zero- and first-order absorption with lag time for the extended-release formulation, and linear elimination adequately described upadacitinib plasma concentration-time profiles. The oral bioavailability of upadacitinib extended-release formulation was estimated to be approximately 80% relative to the immediate-release formulation. Covariates included in the final model were creatinine clearance, subject population (healthy subjects vs subjects with atopic dermatitis, ulcerative colitis, or Crohn's disease vs subjects with rheumatoid arthritis) and sex on apparent oral clearance and sex and body weight on apparent volum...
Source: The Journal of Clinical Pharmacology - Category: Drugs & Pharmacology Authors: Tags: J Clin Pharmacol Source Type: research