title: The pharmacokinetics of the weakly protein-bound anionic compound diatrizoate in serum and synovial fluid of the horse.
abstract: OBJECTIVE
  To establish a pharmacokinetic model for the model drug, sodium diatrizoate (DTZ), allowing joint disappearance kinetics to be estimated from serum appearance kinetics following intra-articular administration, and to calculate the relative joint exposure after intravenous and intra-articular DTZ administration (F(iv/IA)).
  
  
  METHODS
  Each of five horses received an aqueous solution of 3.9 mg/kg sodium diatrizoate both intravenously and intra-articularly separated by a one-week wash out period. Serum and synovial samples were collected over 7 h and analyzed for content of model compound using inductively coupled plasma mass spectrometry.
  
  
  RESULTS
  Differential equations were used for describing the transport of DTZ between the joint and the central compartment. The three-compartment lag-time model obtained demonstrates that the rate of drug appearance in the systemic circulation equals the rate of disappearance from the joint compartment. Following intravenous and intra-articular administration, an average F(iv/IA) of 0.04% (n = 4) was calculated based on the synovial fluid profiles of DTZ.
  
  
  CONCLUSIONS
  This study implies that aspects of the intra-articular fate of DTZ can be obtained from serum data in case synovial fluid samplings are limited, for various possible reasons. The low F(iv/IA) may stimulate future research in the field of intra-articular administration of anti-osteoarthritic drugs.
authors.affiliation: Department of Pharmaceutics and Analytical Chemistry, Faculty of Pharmaceutical Sciences, University of Copenhagen, Universitetsparken 2, DK-2100, Copenhagen Ø, Denmark.
authors.forename: Anna Buus
authors.initials: AB
authors.lastname: Frost
authors.forename: Frank
authors.initials: F
authors.lastname: Larsen
authors.forename: Susan Weng
authors.initials: SW
authors.lastname: Larsen
authors.forename: Jesper
authors.initials: J
authors.lastname: Østergaard
authors.forename: Maj Halling
authors.initials: MH
authors.lastname: Thomsen
authors.forename: Stefan
authors.initials: S
authors.lastname: Stürup
authors.forename: Pia Haubro
authors.initials: PH
authors.lastname: Andersen
authors.forename: Claus
authors.initials: C
authors.lastname: Larsen
mesh_terms: D000818:Animals; D003973:Diatrizoate / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics*; D006736:Horses; D007270:Injections, Intra-Articular; D007275:Injections, Intravenous; D008962:Models, Theoretical; D013582:Synovial Fluid / Q000378:metabolism*; D013997:Time Factors
chemical_list: D003973:Diatrizoate