China
Africa
Explore chapters and articles related to this topic
Small-Molecule Targeted Therapies
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
Ruxolitinib (JakaviTM in the EU, JakafiTM in the US), developed by Novartis after licensing from Incyte, was the first JAK inhibitor to be approved (2011), and this was for the treatment of myelofibrosis. Other JAK/STAT inhibitors have since been developed, but these are mostly for inflammatory diseases. For example, tofacitinib (XeljanzisTM) is used to treat moderate to severe active psoriatic arthritis or rheumatoid arthritis in adults who have failed on methotrexate or related medications. Tofacitinib is sometimes given in combination with methotrexate or other arthritis medicines to treat psoriatic arthritis, rheumatoid arthritis, ankylosing spondylitis, and ulcerative colitis. Other analogues include filgotinib (GLPG0634), which is currently under development by Gilead/Galapagos. The pharmaceutical company Eli Lilly has developed baricitinib (OlumiantTM), which selectively and reversibly inhibits JAK1 and JAK2 and is used to treat rheumatoid arthritis in patients who have had an inadequate response to other anti-rheumatic agents. Finally, AbbVie has developed upadacitinib (RinvoqTM), which, like filgotinib, is a selective and reversible inhibitor of JAK1 and is used mainly for rheumatoid arthritis. However, it has received a black box warning for its potential toxicities. Other examples of agents of this type include oclacitinib (ApoquelTM), used for the control of pruritus associated with allergic dermatitis; peficitinib (SmyrafTM), which mainly inhibits JAK3 and is used for treatment of rheumatoid arthritis; and fedratinib (InrebicTM), a JAK2 inhibitor used for the treatment of primary or secondary myelofibrosis.
Peficitinib for the treatment of rheumatoid arthritis: an overview from clinical trials
Published in Expert Opinion on Pharmacotherapy, 2020
Yoshiya Tanaka, Hiroyuki Izutsu
Peficitinib is absorbed rapidly: after a single dose under fasting conditions, median time to maximum plasma concentration (tmax) was 1.0–1.8 h [55]. The maximum plasma concentration (Cmax) and area under the plasma concentration–time curve (AUC) both showed dose proportionality [55]. Peficitinib can be taken at any time of day but is administered with a meal [20]. After a single oral dose of peficitinib 150 mg was administered in healthy Japanese adults (18 subjects), fed-state administration resulted in a 56.4% increase in Cmax and a 36.8% increase in the area under the plasma concentration–time curve from time zero to time of last measurable concentration (AUClast), compared with fasted-state administration [20]. Following multiple oral doses of peficitinib 150 mg once daily in healthy Japanese adults (24 subjects) after a meal, peficitinib plasma concentrations reached a steady state on day 3; steady-state Cmax and area under the plasma concentration–time curve over 24 h (AUC24h) were 613.2 ng/mL and 2643 ng·h/mL, respectively; and the median (min, max) tmax was 3.0 h (1.5, 4.0) [56]. The accumulation ratio in the steady-state to post single-dose administration was 1.2 [20].