Pharmacokinetics and pharmacodynamics of infliximab, an anti-tumor necrosis factor-alpha monoclonal antibody, following single subcutaneous administrations in rheumatoid arthritis patients

Abstract

Aims To assess the pharmacokinetics (PK) and pharmacodynamics (PD) of infliximab (INFX) prepared in a new highly concentrated formulation following single subcutaneous (SC) injections in rheumatoid arthritis (RA) patients. Methods Patients with active RA were enrolled in a Phase I, open-label, randomized study with single SC doses of INFX (0.5, 1.5 and 3.0 mg/kg, n= 5 per group). Serum INFX levels were measured using ELISA. Non-compartmental analysis was employed to calculate PK parameters. The absolute bioavailability (BA) of INFX was estimated from the dose-normalized AUC following SC injection and a previous clinical trail of INFX as IV infusion. The relationships between PK and the tender joint count (TJC), swollen joint count (SJC) and C-reactive protein (CRP) were also investigated. Results INFX was slowly absorbed into the systemic circulation (median Tmax= 7.0 days) and slowly eliminated from the serum (median T1/2= 8.1 days). The Cmax and AUC increased in a dose-proportional manner, and the T1/2 and CL/F were dose-independent. The BA of INFX was approximately 71.1%. Rapid reductions in TJC, SJC and CRP were seen at all dose levels at week 2 through week 4. The reduction in TJC at week 4 appeared to be a function of the dose and AUC. Conclusions PK of INFX following single SC doses were linear and dose-independent. SC administration is feasible in terms of its BA and clinical response. Note: This new formulation of INFX has not been approved by the FDA or other regulatory agencies for human therapeutic use. Clinical Pharmacology & Therapeutics (2005) 77, P43–P43; doi: 10.1016/j.clpt.2004.12.056