Population Pharmacokinetics of Upadacitinib in Healthy Subjects and Subjects with Rheumatoid Arthritis: Analyses of Phase I and II Clinical Trials.

ABSTRACT:

Background and objectives

Upadacitinib is a janus kinase (JAK) 1 inhibitor being developed for the treatment of rheumatoid arthritis (RA) and other inflammatory diseases. This work characterized upadacitinib population pharmacokinetics in healthy subjects and RA patients and the effects of covariates on upadacitinib exposure.

Methods

Upadacitinib plasma concentrations (n = 6399) from 107 healthy subjects and 466 RA patients from three phase I and two 12-week RA phase IIb trials (1-48 mg immediate-release doses across studies) were analyzed using non-linear mixed-effects modeling. The models were qualified using bootstrap and stochastic simulations.

Results

A two-compartment model with first-order absorption and elimination described upadacitinib pharmacokinetics. Esti

SUBMITTER: Klunder B 

PROVIDER: S-EPMC6028884 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature