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Clinical Pharmacokinetics

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01.12.2015 | Letter to the Editor

Comment on: “Pharmacokinetics and Pharmacokinetic/Pharmacodynamic Modelling of Filgotinib (GLPG0634), a Selective JAK1 Inhibitor, in Support of Phase IIB Dose Selection”

verfasst von: Nuggehally R. Srinivas

Erschienen in: Clinical Pharmacokinetics | Ausgabe 12/2015

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Excerpt

With the recent approval of rofacitinib for the management of moderate to severe rheumatoid arthritis, the inhibition of Janus kinases (JAKs) is being explored for the treatment of inflammatory diseases [1‐3]. Within the JAK-based therapeutic target, it appears that JAK1 inhibition may play an important role in the in vivo efficacy of treatments for several inflammatory diseases [4]. In this context, filgotinib represents a potent JAK1 inhibitor with 30-fold higher selectivity than JAK2 inhibition [5]. Filgotinib undergoes hydrolytic cleavage and forms an active metabolite, the potency of which (11 µmol/L) was reported to be 17-fold lower than that of filgotinib (0.63 µmol/L) [5, 6]. …

O’Shea JJ, Kontzias A, Yamaoko K, Tanaka Y, Laurence A. Janus kinase inhibitors in autoimmune diseases. Ann Rheum Dis. 2013;72(Suppl. 2):111–5.

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Riese RJ, Krishnaswami S, Kremer J. Inhibition of JAK kinases in patients with rheumatoid arthritis: scientific rationale and clinical outcomes. Best Pract Res Clin Rheumatol. 2010;24:513–26.CrossRefPubMed

Haan C, Rolvering C, Raulf F, Kapp M, Druckes P, Thoma G, et al. Jak1 has a dominant role over Jak3 in signal transduction through cc containing cytokine receptors. Chem Biol. 2011;18:314–23.CrossRefPubMed

Van Rompaey L, Galien R, Van der Aar E, Clement-Lacroix P, Nelles L, Smets B, et al. Preclinical characterization of GLPG0634, a selective inhibitor of JAK1 for the treatment of inflammatory diseases. J Immunol. 2013;191(7):3568–77.CrossRefPubMed

Galien R, Vayssière B, De Vos S, Auberval M, Vandeghinste N, Dupont S, et al. Analysis of the JAK1 selectivity of GLPG0634 and its main metabolite in different species, healthy subjects and rheumatoid arthritis patients [abstract no. 478]. San Diego: American College of Rheumatology Annual Meeting; 36–30 Oct 2013.

Namour F, Diderichsen PM, Cox E, Vayssière B, Van der Aa A, Tasset C, et al. Pharmacokinetics and pharmacokinetic/pharmacodynamic modeling of filgotinib (GLPG0634), a selective JAK1 inhibitor, in support of phase IIB dose selection. Clin Pharmacokinet. 2015;54(8):859–74.PubMedCentralCrossRefPubMed

Vanhoutte F, Mazur M, Der Van, Aa A, Wigerinck P, Van’t Klooster G. Selective JAK1 inhibition in the treatment of rheumatoid arthritis: proof of concept with GLPG0634 [abstract]. Arthritis Rheum. 2012;64(Suppl. 10):2489.

Titel: Comment on: “Pharmacokinetics and Pharmacokinetic/Pharmacodynamic Modelling of Filgotinib (GLPG0634), a Selective JAK1 Inhibitor, in Support of Phase IIB Dose Selection”
verfasst von: Nuggehally R. Srinivas
Publikationsdatum: 01.12.2015
Verlag: Springer International Publishing
Erschienen in: Clinical Pharmacokinetics / Ausgabe 12/2015
Print ISSN: 0312-5963
Elektronische ISSN: 1179-1926
DOI: https://doi.org/10.1007/s40262-015-0335-6

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Comment on: “Pharmacokinetics and Pharmacokinetic/Pharmacodynamic Modelling of Filgotinib (GLPG0634), a Selective JAK1 Inhibitor, in Support of Phase IIB Dose Selection”

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