Clin Pharmacokinet
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Randomized Controlled Trial
Population pharmacokinetics of losmapimod in healthy subjects and patients with rheumatoid arthritis and chronic obstructive pulmonary diseases.
Losmapimod is an orally available, potent p38 mitogen-activated protein kinase inhibitor. It is in development as an anti-inflammatory drug in different therapeutic areas. Clinical studies have shown that losmapimod is well tolerated and safe in humans and several studies have shown its pharmacological effect in the target diseases. The aim of this work was to develop a population pharmacokinetic model and to explore the covariates affecting the pharmacokinetics of losmapimod using data collected from healthy volunteers and patients with rheumatoid arthritis (RA) and chronic obstructive pulmonary diseases (COPD). ⋯ The population pharmacokinetic model described in this work well characterized the pharmacokinetic profile of losmapimod following administration of a single oral dose and repeated oral doses in healthy subjects and patients with RA and COPD. Although sex, bodyweight and age were significant factors influencing some pharmacokinetic parameters of losmapimod, the relatively small magnitude of the effect did not result in concerns for dose adjustment.