title: Pharmacokinetic considerations in the treatment of multiple sclerosis with interferon-β.
abstract: BACKGROUND
  Interferon-β (IFNβ) is well established as a disease-modifying treatment for patients with multiple sclerosis. Several preparations of the biopharmaceutical are available differing in protein structure, formulation, dose as well as frequency and route of administration. Recently, a pegylated form of IFNβ has been marketed.
  
  
  METHODS
  Following a PubMed database search, we provide an overview of what is presently known about the pharmacokinetics (PK) of IFNβ including its absorption, distribution, metabolism and elimination. Also, we discuss the association with clinically relevant issues such as treatment efficacy, adverse events and anti-drug antibodies.
  
  
  CONCLUSIONS
  IFNβ has a bioavailability of ∼ 30% after subcutaneous or intramuscular administration, shows peak serum concentrations within several hours, has a half-life of < 1 day and is eliminated by a renal and hepatic pathway. PK parameters do not substantially differ between the types of IFNβ and routes of administration; only pegylation of IFNβ results in substantially increased and prolonged PK. Although no clinical dose-effect relationship could be established, there is an association of IFNβ dose with magnetic resonance imaging outcome parameters. Furthermore, there is an association of IFNβ serum levels with the occurrence of adverse events and anti-drug antibodies.
authors.affiliation: a 1 Innsbruck Medical University, Department of Neurology , Innsbruck, Austria.
authors.forename: Harald
authors.initials: H
authors.lastname: Hegen
authors.affiliation: a 1 Innsbruck Medical University, Department of Neurology , Innsbruck, Austria.
authors.forename: Michael
authors.initials: M
authors.lastname: Auer
authors.affiliation: b 2 Innsbruck Medical University, Department of Neurology, Neuroimmunology Laboratory , Innsbruck, Austria +43 5 12 50 42 42 64 ; +43 5 12 50 42 42 66 ; florian.deisenhammer@tirol-kliniken.at.
authors.forename: Florian
authors.initials: F
authors.lastname: Deisenhammer
mesh_terms: D000818:Animals; D001682:Biological Availability; D004305:Dose-Response Relationship, Drug; D006207:Half-Life; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D016899:Interferon-beta / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D008279:Magnetic Resonance Imaging; D009103:Multiple Sclerosis / Q000188:drug therapy*; D014018:Tissue Distribution
chemical_list: D007155:Immunologic Factors; D016899:Interferon-beta
keywords: flu-like symptoms; interferon-β; multiple sclerosis; neutralizing anti-drug antibodies; pegylation; pharmacokinetics; treatment efficacy