Pharmacokinetics and Pharmacodynamics of IFN-β1a in Healthy Volunteers

Abstract

The pharmacokinetics of recombinant human interferon-β1a (IFN-β1a) (Rebif, Ares-Serono, Geneva, Switzerland) were investigated in healthy volunteers following intravenous (i.v.) administration of increasing single doses of the drug (22 μg/6 million international units [MIU], 44 μg/12 MIU, and 66 μg/18 MIU); i.v., intramuscular (i.m.), and subcutaneous (s.c.) administration of a 66-μg dose; and repeated s.c. administration of four 66-μg doses at 48-h intervals. The disposition of IFN-β1a followed triexponential decay after i.v. administration (half-lives 3 min, 42 min, and 22 h, respectively). After s.c. and i.m. administration, absorption was the rate-limiting factor in the terminal phase. The median absolute bioavailabilities were 30% and 27%, respectively. The accumulation ratio after repeated s.c. injections was 2.4, and a terminal half-life of 66 h was observed. Intracellular 2-5A synthetase activity and serum neopterin and β2-microglobulin concentrations increased after all IFN-β1a injections and remained elevated following every-other-day administration. The local tolerance was good, and the systemic tolerance was satisfactory.