Cytokine Signalling Forum

Publications





December 18

Influencia de la Edad y del Daño Renal en la Farmacocinética de Estado Estable de Filgotinib, un inhibidor selectivo de JAK1

Namour F, Fagard L, Van der AA, Harrison P, Xin Y, Tasset C.
Br J Clin Pharmacol 2018 Dec;84(12):2779-2789. DOI:10.1111/bcp.13726

Age and renal impairment (RI) had limited impact on the pharmacokinetics (PK) of filgotinib (FIL) but, in subjects with severe RI, exposure to the FIL metabolite was increased. FIL is a selective JAK1 inhibitor that is extensively, rapidly and proportionately absorbed after oral dosing from 50–200mg. Its major metabolite has a similar JAK1 selectivity profile but with reduced potency. In humans, exposure to the metabolite is higher by approximately 16–20 fold compared with the pare...

Keywords: JAK, Filgotinib, Preclinical, PK-PD

Translated by: Igor

May 18

Farmacocinética de Upadacitinib con Regímenes Clínicos de Formulación de Liberación Extendida Utilizados en Ensayos Clínicos Fase 3 de Artritis Reumatoide

Mohamed MEF, Zeng J, Marroum PJ, Song IH, Othman AA.
Clin Pharmacol Drug Dev. 2019 Feb;8(2):208-216. doi: 10.1002/cpdd.462

Upadacitinib (UPA) extended release (ER) formulation dosing achieved the target profile that enables single dosing in patients with RA. In early clinical studies, UPA was given as an immediate release (IR) formulation, however patients were noted to experience fluctuations in blood plasma concentrations. To enhance patient compliance in UPA Phase 3 trials, ER tablets have been developed. Here, authors aimed at characterising the pharmacokinetics of UPA single and multiple doses of ER compared ...

Keywords: JAK, Upadacitinib, Preclinical, PK-PD

January 14

Traducción preclínica a clínica de tofacitinib, un inhibidor de la quinasa de Janus, en la artritis reumatoide

Dowty M, Jesson MI, Ghosh S, et al.
J Pharmacol Exp Ther. 2013. DOI:10.1124/jpet.113.209304

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...

Keywords: JAK, Tofacitinib, Preclinical, PK-PD

September 13

Farmacocinética de fostamatinib, un inhibidor de la tirosina quinasa esplénica (SYK) en sujetos humanos sanos después de su administración oral individual y múltiple en tres estudios de fase I

Baluom M, Grossbard EB, Mant T, Lau DTW.
Br J Clin Pharmacol. 2013 Jul;76(1):78–88

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...

Keywords: Cytokine Signalling, Preclinical, PK-PD