title: Drug Interactions Between Peficitinib, an Orally Administered, Once-Daily Janus Kinase Inhibitor, and Rosuvastatin in Healthy Subjects.
abstract: 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.
  
  
  
  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.
  
  
  
  Co-administration of peficitinib with rosuvastatin increased rosuvastatin area under the concentration-time curve (AUC) and maximum plasma concentration (Cmax) by 18 and 15%, respectively and increased peficitinib AUC and Cmaxby 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 Cmaxwas 67 and 34% higher, when administered alone or with rosuvastatin. Peficitinib was well tolerated with few adverse events overall.
  
  
  
  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.
  
  
  
  NCT01959399.
authors.affiliation: Clinical Pharmacology and Exploratory Development, Astellas Pharma Global Development Inc., 1 Astellas Way, Northbrook, IL, 60062, USA. tong.zhu@astellas.com.
authors.forename: Tong
authors.initials: T
authors.lastname: Zhu
authors.affiliation: Clinical Pharmacology and Exploratory Development, Astellas Pharma Global Development Inc., 1 Astellas Way, Northbrook, IL, 60062, USA.
authors.forename: Barbara
authors.initials: B
authors.lastname: Parker
authors.affiliation: Clinical Pharmacology and Exploratory Development, Astellas Pharma Global Development Inc., 1 Astellas Way, Northbrook, IL, 60062, USA.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Wojtkowski
authors.affiliation: Astellas Pharma Inc., Tokyo, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Nishimura
authors.affiliation: Clinical Pharmacology and Exploratory Development, Astellas Pharma Global Development Inc., 1 Astellas Way, Northbrook, IL, 60062, 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: Clinical Pharmacology and Exploratory Development, Astellas Pharma Global Development Inc., 1 Astellas Way, Northbrook, IL, 60062, USA.
authors.forename: James
authors.initials: J
authors.lastname: Keirns
mesh_terms: D000218:Adamantane / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology; D000284:Administration, Oral; D000328:Adult; D004347:Drug Interactions; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D000075242:Janus Kinase Inhibitors / Q000009:adverse effects / Q000494:pharmacology*; D027381:Liver-Specific Organic Anion Transporter 1 / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009536:Niacinamide / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology; D000068718:Rosuvastatin Calcium / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D055815:Young Adult
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000075242:Janus Kinase Inhibitors; D027381:Liver-Specific Organic Anion Transporter 1; C503999:SLCO1B1 protein, human; D009536:Niacinamide; D000068718:Rosuvastatin Calcium; C000608065:peficitinib; D000218:Adamantane