Publications

View and download slide summaries of the latest original articles focusing on therapies in immune-mediated inflammatory diseases including rheumatology, dermatology, and gastroenterology. All materials produced by the team are subsequently reviewed and approved by individual Steering Committee members.

February 2014

The Pharmacokinetics, Metabolism, and Clearance Mechanisms of Tofacitinib, a Janus Kinase Inhibitor, in Humans

DMD doi:10.1124/dmd.113.054940

Dowty ME,

Lin J,

Ryder TF et al

The PK of tofacitinib has previously been described in several papers covering a range of diseases. This current study was used to better understand the PK, metabolism and clearance mechanisms of tofacitinib in healthy human subjects. Six subjects took a single 50mg dose of 14C-tofacitinib orally and consequently had urine, faeces and plasma collected. These were assayed for radioactivity and profiled for metabolites. Tofacitinib was found to be rapidly absorbed, with peak plasma concentrations ...

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January 2014

Preclinical to Clinical Translation of Tofacitinib, a Janus Kinase Inhibitor, in Rheumatoid Arthritis

J Pharmacol Exp Ther. 2013. DOI:10.1124/jpet.113.209304

Dowty M,

Jesson MI,

Ghosh S,

et al.

Preclinical studies can provide insight into mechanisms of efficacy and optimal dosing regimens. In this study, Dowty et al. compare the pharmacokinetic / pharmacodynamic profiles of tofacitinib in a murine arthritis model and in patients with rheumatoid arthritis from tofacitinib clinical trials. The main driver of efficacy in both preclinical murine arthritis models and clinical RA was found to be inhibition of JAK1 heterodimer signalling, where total drug exposure (Cave) was a predictor of pr...

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September 2013

Pharmacokinetics of fostamatinib, a spleen tyrosine kinase (SYK) inhibitor, in healthy human subjects following single and multiple oral dosing in three phase I studies

Br J Clin Pharmacol. 2013 Jul;76(1):78–88

Baluom M,

Grossbard EB,

Mant T,

Lau DTW

Fostamatinib (R778) is a prodrug designed to deliver the active metabolite R406 which is an inhibitor of SYK and is currently under investigation for treatment of RA. The three clinical trials, conducted in healthy subjects, included two ascending dose studies and a formulation study. The first was a single ascending dose of R406, from 80-600mg, the second was a single and multiple dose study of fostamatinib in aqueous solution with single doses from 80-400mg and multiple doses of 160mg twice da...