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Home / Equine Research Bank / Pharm Res / The pharmacokinetics of the weakly protein-bound anionic com...
Pharmaceutical research2009; 27(1); 143-150; doi: 10.1007/s11095-009-9988-x

The pharmacokinetics of the weakly protein-bound anionic compound diatrizoate in serum and synovial fluid of the horse.

Abstract: 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.
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Publication Date: 2009-10-30 PubMed ID: 19876722DOI: 10.1007/s11095-009-9988-xGoogle Scholar: Lookup
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  • Comparative Study
  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This research study focuses on the pharmacokinetics of an anionic compound called sodium diatrizoate (DTZ) in horses. The aim was to develop a model to predict the drug’s behavior within the joint, based on the drug concentration found in blood serum, after both intravenous and intra-articular administration.

Methodology

  • The researchers employed a total of five horses, each infused with an aqueous solution of sodium diatrizoate, first intravenously and then intra-articularly. This was done with a one-week gap to allow for complete elimination of the drug (wash-out period).
  • Blood serum and synovial fluid samples were collected over a period of 7 hours and were analyzed using inductively coupled plasma mass spectrometry to determine the concentration of the administered drug.

Results and Interpretation

  • To describe the transport of DTZ between the joint and the systemic circulation, the researchers used mathematical modelling in the form of differential equations. This resulted in a three-compartment lag-time model that included the joint, the central blood compartment, and various ‘peripheral’ compartments.
  • The model showed that the rate of appearance of the drug in the systemic circulation was equal to the rate of disappearance of the drug from the joint. This implies a direct relationship between the two.
  • By comparing the concentration profiles of DTZ in the synovial fluid following intravenous and intra-articular administration, the researchers calculated an average relative joint exposure (Fiv/IA) of 0.04%. This value indicates that only a small fraction of the drug given intravenously reaches the joint.

Conclusions

  • The findings suggest that synovial fluid samples are not necessarily needed to predict the behavior of a drug within the joint. The same information can be inferred from serum data, which is easier to obtain.
  • The low F(iv/IA) suggests that the majority of a drug administered intravenously may not reach the joint, which may stimulate further research on the efficiency and utility of intra-articular drug administration, particularly for the treatment of joint-related diseases such as osteoarthritis.

Cite This Article

APA
Frost AB, Larsen F, Larsen SW, Østergaard J, Thomsen MH, Stürup S, Andersen PH, Larsen C. (2009). The pharmacokinetics of the weakly protein-bound anionic compound diatrizoate in serum and synovial fluid of the horse. Pharm Res, 27(1), 143-150. https://doi.org/10.1007/s11095-009-9988-x

Publication

Pharmaceutical research
ISSN: 1573-904X
NlmUniqueID: 8406521
Country: United States
Language: English
Volume: 27
Issue: 1
Pages: 143-150

Researcher Affiliations

Frost, Anna Buus
  • Department of Pharmaceutics and Analytical Chemistry, Faculty of Pharmaceutical Sciences, University of Copenhagen, Universitetsparken 2, DK-2100, Copenhagen Ø, Denmark.
Larsen, Frank
    Larsen, Susan Weng
      Østergaard, Jesper
        Thomsen, Maj Halling
          Stürup, Stefan
            Andersen, Pia Haubro
              Larsen, Claus

                MeSH Terms

                • Animals
                • Diatrizoate / administration & dosage
                • Diatrizoate / blood
                • Diatrizoate / pharmacokinetics
                • Horses
                • Injections, Intra-Articular
                • Injections, Intravenous
                • Models, Theoretical
                • Synovial Fluid / metabolism
                • Time Factors

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                Citations

                This article has been cited 1 times.
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