Clin Pharmacokinet
-
Randomized Controlled Trial
Pharmacokinetics and Pharmacokinetic/Pharmacodynamic Modeling of Filgotinib (GLPG0634), a Selective JAK1 Inhibitor, in Support of Phase IIB Dose Selection.
Filgotinib (GLPG0634) is a selective inhibitor of Janus kinase 1 (JAK1) currently in development for the treatment of rheumatoid arthritis and Crohn's disease. While less selective JAK inhibitors have shown long-term efficacy in treating inflammatory conditions, this was accompanied by dose-limiting side effects. Here, we describe the pharmacokinetics of filgotinib and its active metabolite in healthy volunteers and the use of pharmacokinetic-pharmacodynamic modeling and simulation to support dose selection for phase IIB in patients with rheumatoid arthritis. ⋯ Based on these results, a daily dose range up to 200 mg has been selected for phase IIB dose-finding studies in patients with rheumatoid arthritis.
-
Tramadol hydrochloride is used worldwide as an analgesic drug with a unique dual function. The metabolic enzymes cytochrome P450 (CYP) 3A4, CYP2B6, and CYP2D6 and the various transporters [adenosine triphosphate-binding cassette B1/multidrug resistance 1/P-glycoprotein, organic cation transporter 1, serotonin transporter (SERT), norepinephrine transporter (NET)] and receptor genes (opioid receptor μ 1 gene) give possible genetic differences that might affect the pharmacokinetics and/or pharmacodynamics of tramadol. Therefore, the aim of this review is to present a systematic walkthrough of all possible genetic factors involved in the pharmacology of tramadol. ⋯ In this systematic review, the current knowledge on all possible genetic factors that might influence the metabolism or clinical efficacy of tramadol has been collected and summarized. Only the effect of CYP2D6 polymorphisms on the metabolism of tramadol and the consequent effect on pain relief has been thoroughly studied and sufficiently established as clinically relevant.