Pharmacokinetics and pharmacodynamics of IFN-beta 1a in healthy volunteers.
The pharmacokinetics of recombinant human interferon-beta1a (IFN-beta1a) (Rebif, Ares-Serono, Geneva, Switzerland) were investigated in healthy volunteers following intravenous (i.v.) administration of increasing single doses of the drug (22 microg/6 million international units [MIU], 44 microg/12 MIU, and 66 microg/18 MIU); i.v., intramuscular (i.m.), and subcutaneous (s.c.) administration of a 66-microg dose; and repeated s.c. administration of four 66-microg doses at 48-h intervals. The disposition of IFN-beta1a 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 beta2-microglobulin concentrations increased after all IFN-beta1a injections and remained elevated following every-other-day administration. The local tolerance was good, and the systemic tolerance was satisfactory.
Buchwalder
P A
PA
Division of Clinical Pharmacology, Department of Medicine, University Hospital of Lausanne, Switzerland.
Buclin
T
T
Trinchard
I
I
Munafo
A
A
Biollaz
J
J
D000293:Adolescent; D000328:Adult; D019540:Area Under Curve; D005260:Female; D006801:Humans; D007273:Injections, Intramuscular; D007275:Injections, Intravenous; D007370:Interferon Type I / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology; D016899:Interferon-beta / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology*; D008297:Male; D020714:Maximum Tolerated Dose; D011994:Recombinant Proteins
D007370:Interferon Type I; D011994:Recombinant Proteins; D016899:Interferon-beta