Pharmacokinetics and pharmacodynamics of IFN-β1a in healthy volunteers

The pharmacokinetics of recombinant human interferon-beta 1a (IFN-beta 1a) (Rebif, Ares-Serono, Geneva, Switzerland) were investigated in healthy volunteers following intravenous (i.v.) administration of increasing single doses of the drug (22 mug/6 million international units [MIU], 44 mug/12 MIU, and 66 mug/18 MIU); i.v., intramuscular (i.m.), and subcutaneous (s.c.) administration of a 66-mug dose; and repeated s.c. administration of four 66-mug doses at 48-h intervals. The disposition of IFN-beta 1a 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 beta (2)-microglobulin concentrations increased after all IFN-beta 1a injections and remained elevated following every-other-day administration. The local tolerance was good, and the systemic tolerance was satisfactory.