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Pharmacokinetics of tofacitinib, a janus kinase inhibitor, in patients with impaired renal function and end‐stage renal disease
Author(s) -
Krishnaswami Sriram,
Chow Vincent,
Boy Mary,
Wang Cunshan,
Chan Gary
Publication year - 2014
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1002/jcph.178
Subject(s) - medicine , janus kinase inhibitor , pharmacokinetics , renal function , urology , tofacitinib , hemodialysis , end stage renal disease , dialysis , cmax , renal replacement therapy , dosing , creatinine , transplantation , rheumatoid arthritis
The pharmacokinetics (PK) of tofacitinib were assessed in patients with mild (Cockcroft–Gault creatinine clearance >50 and ≤80 mL/min), moderate (≥30 and ≤50 mL/min), and severe (<30 mL/min) renal impairment, and end‐stage renal disease (ESRD) requiring dialysis. Six patients each with normal, mild, moderate, or severely impaired renal function, and 12 patients with ESRD, received single tofacitinib doses of 10 mg. PK data were obtained from blood and dialyzate (patients with ESRD only) samples prior and subsequent to dosing and/or hemodialysis (patients with ESRD only). Relative to patients with normal renal function, mean (90% CI) AUC (0–∞) ratios were 137% (97–195), 143% (101–202), and 223% (157–316) in patients with mild, moderate, and severe renal impairment, respectively. Maximum plasma concentrations (C max ) were similar across the four treatment groups. Terminal phase half‐life (t 1/2 ) increased with severity of renal impairment. Mean AUC (0–∞) in patients with ESRD on a non‐dialysis day was similar to that in patients with moderate renal impairment and approximately 40% greater than healthy volunteer data. Mean (SD) dialyzer efficiency (ratio of dialyzer clearance/blood flow entering the dialyzer) was 0.73 (0.15). However, due to extensive non‐renal clearance, dialysis procedure is unlikely to result in significant elimination of tofacitinib.