TY - JOUR
T1 - The pharmacokinetics of the weakly protein-bound anionic compound diatrizoate in serum and synovial fluid of the horse
AU - Frost, Anna Buus
AU - Larsen, Frank
AU - Larsen, Susan Weng
AU - Østergaard, Jesper
AU - Thomsen, Maj Halling
AU - Stürup, Stefan
AU - Andersen, Pia Haubro
AU - Larsen, Claus Selch
PY - 2010/1
Y1 - 2010/1
N2 - 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.
AB - 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.
KW - Former Faculty of Pharmaceutical Sciences
U2 - 10.1007/s11095-009-9988-x
DO - 10.1007/s11095-009-9988-x
M3 - Journal article
C2 - 19876722
SN - 0724-8741
VL - 27
SP - 143
EP - 150
JO - Pharmaceutical Research
JF - Pharmaceutical Research
IS - 1
ER -