Pharmacokinetics of the Weakly Protein-Bound Anionic Compound Diatrizoate in Serum and Synovial Fluid of the Horse

• Published in: Pharmaceutical research 2010-01, Vol.27 (1), p.143-150
• Main Authors: Frost, Anna Buus, Larsen, Frank, Larsen, Susan Weng, Østergaard, Jesper, Thomsen, Maj Halling, Stürup, Stefan, Andersen, Pia Haubro, Larsen, Claus
• Format: Article
• Language: English
• Subjects: Animals; Aqueous solutions; Biochemistry; Biological and medical sciences; Biomedical and Life Sciences; Biomedical Engineering and Bioengineering; Biomedicine; Diatrizoate - administration & dosage; Diatrizoate - blood; Diatrizoate - pharmacokinetics; Drug delivery systems; Feline immunodeficiency virus; General pharmacology; Horses; Injections, Intra-Articular; Injections, Intravenous; Medical Law; Medical sciences; Models, Theoretical; Pharmaceutical sciences; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Pharmacology/Toxicology; Pharmacy; Proteins; Reaction kinetics; Research Paper; Synovial Fluid - metabolism; Time Factors
• ISSN: 0724-8741; 1573-904X
• DOI: 10.1007/s11095-009-9988-x

Purpose 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 (Fiv/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 Fiv/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 Fiv/IA may stimulate future research in the field of intra-articular administration of anti-osteoarthritic drugs.