Abstract
Background and objective
Peficitinib is an orally administered, once-daily Janus kinase inhibitor in development for the treatment of rheumatoid arthritis. Peficitinib and its major metabolite H2 inhibit the hepatic uptake transporter organic anion transporting polypeptide 1B1 (OATP1B1) in vitro. This article reports a clinical study evaluating the effects of peficitinib on the pharmacokinetics of rosuvastatin, a substrate for the OATP1B1 transporter, and vice versa.
Methods
In an open-label, single-sequence clinical study, 24 healthy adults of East Asian and non-East Asian origin received a single dose of rosuvastatin 10 mg on days 1 and 10. On days 5–13, subjects received a daily dose of 150 mg peficitinib. Serial blood samples for pharmacokinetic assessment of rosuvastatin were collected up to 96 h post-dose on days 1 and 10, and for peficitinib were collected up to 24 h post-dose on days 9 and 10.
Results
Co-administration of peficitinib with rosuvastatin increased rosuvastatin area under the concentration-time curve (AUC) and maximum plasma concentration (C max) by 18 and 15%, respectively and increased peficitinib AUC and C max by 16 and 28%, respectively. In East Asian (n = 6) vs. non-East Asian subjects (n = 18), peficitinib mean AUC for a dosing interval was 45 and 21% higher, and mean C max was 67 and 34% higher, when administered alone or with rosuvastatin. Peficitinib was well tolerated with few adverse events overall.
Conclusion
In this study, once-daily oral administration of peficitinib had no clinically significant effect on the pharmacokinetics of rosuvastatin, a probe substrate for OATP1B1. Therefore, it is unlikely that peficitinib will have a clinically significant effect on the exposure of other substrates for OATP1B1.
ClinicalTrials.gov number
NCT01959399.
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Acknowledgements
Medical writing support was provided by Matthew Reynolds and Victoria Jones of Choice Healthcare Solutions and funded by Astellas Pharma Inc. We acknowledge all other investigators for their participation in this trial.
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This study was funded by Astellas Pharma Inc.
Conflict of interest
Tong Zhu, Tomasz Wojtkowski, Tetsuya Nishimura, and James Keirns are employees of Astellas Pharma Inc. Barbara Parker, Jay Garg, and Ogert Fisniku were employees of Astellas Pharma Inc. during the study. David Han is an employee of PAREXEL International, contracted by Astellas Pharma Inc. to conduct the clinical assessments throughout this study.
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Zhu, T., Parker, B., Wojtkowski, T. et al. Drug Interactions Between Peficitinib, an Orally Administered, Once-Daily Janus Kinase Inhibitor, and Rosuvastatin in Healthy Subjects. Clin Pharmacokinet 56, 747–757 (2017). https://doi.org/10.1007/s40262-016-0474-4
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DOI: https://doi.org/10.1007/s40262-016-0474-4