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The effect of mild and moderate hepatic impairment on the pharmacokinetics of tofacitinib, an orally active Janus kinase inhibitor
Author(s) -
Lawendy Nervin,
Lamba Manisha,
Chan Gary,
Wang Rong,
Alvey Christine W.,
Krishnaswami Sriram
Publication year - 2014
Publication title -
clinical pharmacology in drug development
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.711
H-Index - 22
eISSN - 2160-7648
pISSN - 2160-763X
DOI - 10.1002/cpdd.143
Subject(s) - tofacitinib , janus kinase inhibitor , medicine , orally active , pharmacokinetics , janus kinase , pharmacology , oral administration , receptor , rheumatoid arthritis
Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis. We report here an evaluation of the pharmacokinetics of a single 10 mg dose of tofacitinib in healthy volunteers (n = 6) and subjects with mild (n = 6) or moderate (n = 6) hepatic impairment. Compared to healthy volunteers, tofacitinib area under the plasma concentration–time profile from time 0 to infinity (AUC inf ) and maximum observed concentration (C max ) in subjects with mild hepatic impairment were not altered. In subjects with moderate hepatic impairment, the geometric mean AUC inf and C max of tofacitinib were increased (90% confidence intervals of percentage increase) by approximately 65% (25%, 117%) and 49% (12%, 97%), respectively. A single dose of tofacitinib 10 mg resulted in two treatment‐emergent adverse events (AE) in the mild hepatic impairment group, and one in the moderate hepatic impairment group; they were not considered related to study treatment. There were no deaths, serious AEs, discontinuations due to AEs, or dose reductions due to AEs. Data from this study were critical to deriving dose adjustments for subjects with hepatic impairment.