title: Effects of interleukin-1 receptor antagonist in a slow-release hylan vehicle on rat type II collagen arthritis.
abstract: OBJECTIVE
  To determine the effect of hylan fluid (HA), a model slow release vehicle on the pharmacokinetic profile and efficacy of interleukin-1 receptor antagonist (IL-1ra) in rats with established type II collagen arthritis.
  
  
  METHODS
  Female Lewis rats with type II collagen arthritis were treated daily, every other day or every third day with single subcutaneous (sc) injections of IL-1ra formulated in HA and the effects on arthritis determined. Results were compared to those obtained with IL-1ra in citrate buffered saline with EDTA and polysorbate (CSEP). Sequential blood levels were determined in rats injected sc with IL-1ra in CSEP or HA.
  
  
  RESULTS
  Incorporation into HA led to slower release of IL-1ra into the bloodstream and maintained therapeutic blood levels of IL-1ra for a longer time compared to the IL-1ra/CSEP formulation. Single daily sc doses of 100 mg/kg IL-1ra in CSEP were ineffective in type II collagen arthritis. By contrast, once per day dosing of 100 mg/kg IL-1ra in HA provided 78% inhibition of paw swelling. Every other day dosing with 100 mg/kg IL-1ra in HA resulted in 62% inhibition. IL-1ra (100 mg/ kg in HA) given every third day provided 19% inhibition of arthritis. Improved efficacy correlated with improved pharmacokinetics.
  
  
  CONCLUSIONS
  Administration of IL-1ra in the slow release vehicle HA improves pharmacokinetics and efficacy in rat type II collagen arthritis.
authors.affiliation: Amgen Inc., Thousand Oaks, California 91320-1789, USA.
authors.forename: A
authors.initials: A
authors.lastname: Bendele
authors.forename: T
authors.initials: T
authors.lastname: McAbee
authors.forename: M
authors.initials: M
authors.lastname: Woodward
authors.forename: J
authors.initials: J
authors.lastname: Scherrer
authors.forename: D
authors.initials: D
authors.lastname: Collins
authors.forename: J
authors.initials: J
authors.lastname: Frazier
authors.forename: E
authors.initials: E
authors.lastname: Chlipala
authors.forename: D
authors.initials: D
authors.lastname: McCabe
mesh_terms: D000818:Animals; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D003094:Collagen / Q000276:immunology*; D005260:Female; D006820:Hyaluronic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives*; D053590:Interleukin 1 Receptor Antagonist Protein; D014677:Pharmaceutical Vehicles; D051381:Rats; D011917:Rats, Inbred Lew; D012795:Sialoglycoproteins / Q000008:administration & dosage*
chemical_list: D053590:Interleukin 1 Receptor Antagonist Protein; D014677:Pharmaceutical Vehicles; D012795:Sialoglycoproteins; C049816:hylan; D006820:Hyaluronic Acid; D003094:Collagen