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Clinical Pharmacokinetics
Published in: Clinical Pharmacokinetics 7/2017

01-07-2017 | Original Research Article

Drug Interactions Between Peficitinib, an Orally Administered, Once-Daily Janus Kinase Inhibitor, and Rosuvastatin in Healthy Subjects

Authors: Tong Zhu, Barbara Parker, Tomasz Wojtkowski, Tetsuya Nishimura, Jay P. Garg, David Han, Ogert Fisniku, James Keirns

Published in: Clinical Pharmacokinetics | Issue 7/2017

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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.
Appendix
Available only for authorised users
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Metadata
Title
Drug Interactions Between Peficitinib, an Orally Administered, Once-Daily Janus Kinase Inhibitor, and Rosuvastatin in Healthy Subjects
Authors
Tong Zhu
Barbara Parker
Tomasz Wojtkowski
Tetsuya Nishimura
Jay P. Garg
David Han
Ogert Fisniku
James Keirns
Publication date
01-07-2017
Publisher
Springer International Publishing
Published in
Clinical Pharmacokinetics / Issue 7/2017
Print ISSN: 0312-5963
Electronic ISSN: 1179-1926
DOI
https://doi.org/10.1007/s40262-016-0474-4

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