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 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.

• Authors: Tong Zhu, Corrie Howieson, Tomasz Wojtkowski, Jay P Garg, David Han, Ogert Fisniku, James Keirns
• Journal: Clinical pharmacology in drug development (Clin Pharmacol Drug Dev) Vol. 6 Issue 6 Pg. 548-555 (Nov 2017) ISSN: 2160-7648 [Electronic] United States
• PMID: 28301084 (Publication Type: Clinical Trial, Journal Article)
• Copyright: © 2017, The American College of Clinical Pharmacology.

Chemical References

• ATP Binding Cassette Transporter, Subfamily B, Member 1
• Anti-Arrhythmia Agents
• Janus Kinase Inhibitors
• Niacinamide
• Verapamil
• peficitinib
• Adamantane

Topics

• ATP Binding Cassette Transporter, Subfamily B, Member 1 (antagonists & inhibitors)
• Adamantane (administration & dosage, adverse effects, analogs & derivatives, pharmacokinetics)
• Administration, Oral
• Adult
• Anti-Arrhythmia Agents (administration & dosage, adverse effects, pharmacology)
• Area Under Curve
• Cross-Over Studies
• Drug Interactions
• Female
• Humans
• Janus Kinase Inhibitors (administration & dosage, adverse effects, pharmacokinetics)
• Male
• Middle Aged
• Niacinamide (administration & dosage, adverse effects, analogs & derivatives, pharmacokinetics)
• Verapamil (administration & dosage, adverse effects, pharmacology)
• Young Adult