Drug Interactions Between Peficitinib, an Orally Administered, Once-Daily Janus Kinase Inhibitor, and Rosuvastatin in Healthy Subjects
| Autor: | Tomasz Wojtkowski, Tetsuya Nishimura, David Han, Tong Zhu, Ogert Fisniku, Barbara Parker, Jay P. Garg, James Keirns |
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| Rok vydání: | 2016 |
| Předmět: |
Adult
Male Niacinamide Metabolite Administration Oral Adamantane Pharmacology 030226 pharmacology & pharmacy 03 medical and health sciences chemistry.chemical_compound Young Adult 0302 clinical medicine Pharmacokinetics Oral administration medicine Humans Janus Kinase Inhibitors Pharmacology (medical) Rosuvastatin Drug Interactions Rosuvastatin Calcium Adverse effect Janus kinase inhibitor 030203 arthritis & rheumatology biology business.industry Liver-Specific Organic Anion Transporter 1 nutritional and metabolic diseases Middle Aged medicine.disease Healthy Volunteers Organic anion-transporting polypeptide chemistry Rheumatoid arthritis biology.protein Female Hydroxymethylglutaryl-CoA Reductase Inhibitors business medicine.drug |
| Zdroj: | Clinical pharmacokinetics. 56(7) |
| ISSN: | 1179-1926 |
| Popis: | 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 (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. 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. NCT01959399. |
| Databáze: | OpenAIRE |
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