title: The Effect of Verapamil, a P-Glycoprotein Inhibitor, on the Pharmacokinetics of Peficitinib, an Orally Administered, Once-Daily JAK Inhibitor.
abstract: 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 Cmaxby 27%, 27%, and 39%, respectively, and also increased the mean AUC and Cmaxof 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.
authors.affiliation: Astellas Pharma Global Development Inc., Northbrook, IL, USA.
authors.forename: Tong
authors.initials: T
authors.lastname: Zhu
authors.affiliation: Astellas Pharma Global Development Inc., Northbrook, IL, USA.
authors.forename: Corrie
authors.initials: C
authors.lastname: Howieson
authors.affiliation: Astellas Pharma Global Development Inc., Northbrook, IL, USA.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Wojtkowski
authors.affiliation: Astellas Pharma Global Development Inc., Northbrook, IL, USA.
authors.forename: Jay P
authors.initials: JP
authors.lastname: Garg
authors.affiliation: California Clinical Trials, PAREXEL International, Glendale, CA, USA.
authors.forename: David
authors.initials: D
authors.lastname: Han
authors.affiliation: Astellas Research Institute of America LLC, Skokie, IL, USA.
authors.forename: Ogert
authors.initials: O
authors.lastname: Fisniku
authors.affiliation: Astellas Pharma Global Development Inc., Northbrook, IL, USA.
authors.forename: James
authors.initials: J
authors.lastname: Keirns
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors*; D000218:Adamantane / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D000284:Administration, Oral; D000328:Adult; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology; D019540:Area Under Curve; D018592:Cross-Over Studies; D004347:Drug Interactions; D005260:Female; D006801:Humans; D000075242:Janus Kinase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D008297:Male; D008875:Middle Aged; D009536:Niacinamide / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D014700:Verapamil / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D055815:Young Adult
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000889:Anti-Arrhythmia Agents; D000075242:Janus Kinase Inhibitors; D009536:Niacinamide; D014700:Verapamil; C000608065:peficitinib; D000218:Adamantane
keywords: JAK inhibitor; P-glycoprotein inhibitor; peficitinib; pharmacokinetics; verapamil