Bioavailability of adalimumab following subcutaneous injections in rheumatoid arthritis patients

Abstract

Aim To assess bioavailability (BA) of adalimumab following subcutaneous (sc) injections in rheumatoid arthritis (RA) patients using a sparse sampling approach. Methods Blood samples were collected at selected visits up to 2.5 years from a Phase I, multi-center, randomized study in 54 adult RA patients on stable doses of MTX. Patients (18 per group) received either: a) 1 mg/kg sc adalimumab, b) 1 mg/kg iv adalimumab, or c) placebo. The same treatment was repeated in~ 4 weeks, and 4 weeks later, all groups received 1 mg/kg sc open-label dosing every other week for 2.5 years. Serum adalimumab concentrations were measured using an immunoassay. Population pharmacokinetic (PK) analyses were performed using NONMEM software. Results A two-compartment population PK model was used. The population estimate of absolute BA of adalimumab following the sc route was 58%. The mean (CV%) of individual post-hoc CL and Vss were 11.2 mL/h (54.6%) and 6.0L (16.2%), respectively. Conclusions The absolute BA of adalimumab following sc administration in patients on stable methotrexate therapy was approximately 58%. Adalimumab kinetics appeared to be linear and time invariant over 2.5 years. Clinical Pharmacology & Therapeutics (2005) 77, P84–P84; doi: 10.1016/j.clpt.2004.12.212