Pharmacokinetics and pharmacodynamics of tocilizumab, a humanized anti-interleukin-6 receptor monoclonal antibody, following single-dose administration by subcutaneous and intravenous routes to healthy subjects.

摘要: Objectives Tocilizumab, a humanized anti-interleukin-6 receptor (IL-6R) monoclonal antibody, given by intravenous (i.v.) infusion every 4 weeks has been approved for treatment of patients with rheumatoid arthritis. The objective the study was to determine pharmacokinetics (PK) and pharmacodynamics (PD) tocilizumab including absolute PK PD bioavailabilities following subcutaneous (s.c.) administration. Methods 162 mg or 81 after single s.c. i.v. administration were evaluated in an open-label, 4-parallel group involving 48 healthy subjects (n = 12/group). Results Following single-dose tocilizumab, area under serum concentration-time curve (AUC∞) increased 6.4-fold, maximum concentration (Cmax) 4-fold, as dose doubled from mg. Tocilizumab bioavailability (AUC∞ ratio (s.c./i.v.)) higher at (48.8%) than (22.7%). soluble IL-6R (sIL-6R) (AUClast 109% 80.9% C-reactive protein (CRP) effect 98.2% (CRP AUC480h ratio) 80.4% (AUC240h well tolerated both doses Conclusions vs. low; however, effects sIL-6R CRP levels comparable 162-mg Therefore, is based on bioavailability.