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Influence of Age and Renal Impairment on the Steady State Pharmacokinetics of Filgotinib, a Selective JAK1 Inhibitor

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 parent FIL. FIL and its metabolite are predominantly eliminated in urine.

This study investigated the effects of age and renal impairment on the pharmacokinetics (PK) of filgotinib (FIL) and its major metabolite.

The effect of age was examined in two groups of elderly healthy subjects and a control group of younger healthy subjects. The influence of RI was investigated in three groups with mild, moderate and severe RI, plus a control group with normal renal function. The PK of FIL and its metabolite were evaluated over 10 days of FIL 100 mg QD dosing.
The exposure of FIL and its metabolite, at steady state, were moderately higher in elderly subjects compared with younger subjects. FIL and its metabolite’s renal clearance decreased with the degree of RI. The maximum increases in exposure in AUC0-24h were 1.54-fold for FIL, and 2.74-fold for the metabolite, in subjects with severe RI.

Age and mild-to-moderate impairment of renal function had limited impact on the PK of FIL. In subjects with severe RI, the exposure to the metabolite of FIL was elevated, consistent with its renal elimination pathway. It is important to note that this study used FIL 100 mg QD; Phase 3 FINCH studies are also investigating FIL 200 mg QD.

Keywords: JAK, Filgotinib, Preclinical, PK-PD

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Upload date: December 2018

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