Peficitinib is an orally administered, once-daily Janus kinase inhibitor currently in development for the treatment of rheumatoid arthritis. It has been shown to be a P-glycoprotein (P-gp) substrate in vitro. The effects of verapamil, an inhibitor of the efflux pump P-gp, on the pharmacokinetic profile of peficitinib were assessed in this open-label, single-center, single-sequence, crossover drug-interaction study. Twenty-four healthy volunteers received a single 150-mg dose of peficitinib on days 1 and 12 of a 14-day treatment period and received verapamil 80 mg 3 times daily on days 5-14. Repeated-dose administration of verapamil increased mean peficitinib AUCinf , AUClast , and Cmax by 27%, 27%, and 39%, respectively, and also increased the mean AUC and Cmax of peficitinib metabolites H1, H2, and H4. Coadministration of verapamil with peficitinib 150 mg was generally well tolerated. Overall, the most commonly reported adverse event was headache, which occurred in 5 subjects (21%); all reported adverse events were grade 1 severity, with the exception of 1 grade 2 incident of vomiting.
Keywords: JAK inhibitor; P-glycoprotein inhibitor; peficitinib; pharmacokinetics; verapamil.
© 2017, The American College of Clinical Pharmacology.