Synovial Concentration of Trimethoprim-Sulphadiazine Following Regional Limb Perfusion in Standing Horses
The aim of this study was to investigate the safety and pharmacokinetics of trimethoprim-sulphadiazine administered via intravenous regional limb perfusion (IVRLP) into the cephalic vein. According to the hypothesis, the drug could be administered without adverse effects and the synovial concentrati...
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doaj-af02f59b6a184765a54c7363c8e0d0d32021-07-23T13:27:43ZengMDPI AGAnimals2076-26152021-07-01112085208510.3390/ani11072085Synovial Concentration of Trimethoprim-Sulphadiazine Following Regional Limb Perfusion in Standing HorsesKajsa Gustafsson0Amos J. Tatz1Roee Dahan2Wiessam Abu Ahmad3Malka Britzi4Gila A. Sutton5Gal Kelmer6Department of Large Animal Medicine and Surgery, Koret School of Veterinary Medicine, The Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Rehovot 76100, IsraelDepartment of Large Animal Medicine and Surgery, Koret School of Veterinary Medicine, The Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Rehovot 76100, IsraelDepartment of Large Animal Medicine and Surgery, Koret School of Veterinary Medicine, The Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Rehovot 76100, IsraelFaculty of Medicine, Hebrew University-Hadassah Braun School of Public Health and Community Medicine, Jerusalem 9112102, IsraelNational Residue Control Laboratory, Kimron Veterinary Institute, Bet Dagan 50250, IsraelDepartment of Large Animal Medicine and Surgery, Koret School of Veterinary Medicine, The Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Rehovot 76100, IsraelDepartment of Large Animal Medicine and Surgery, Koret School of Veterinary Medicine, The Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Rehovot 76100, IsraelThe aim of this study was to investigate the safety and pharmacokinetics of trimethoprim-sulphadiazine administered via intravenous regional limb perfusion (IVRLP) into the cephalic vein. According to the hypothesis, the drug could be administered without adverse effects and the synovial concentrations would remain above the minimum inhibitory concentration (MIC) for trimethoprim-sulphadiazine (0.5 and 9.5 µg/mL) for 24 h. Ten (<i>n</i> = 10) horses underwent cephalic vein IVRLP with an Esmarch tourniquet applied for 30 min. Four grams (4 g) of trimethoprim-sulphadiazine (TMP-SDZ) were diluted at 0.9% NaCl for a total volume of 100 mL. Synovial fluid and blood samples were obtained immediately before IVRLP and at 0.25, 0.5, 2, 6, 12 and 24 h after the initiation of IVRLP. Trimethoprim and sulphadiazine concentrations were determined using a method based on liquid chromatography/tandem mass spectrometry. The C<sub>max</sub> (peak drug concentration) values were 36 ± 31.1 and 275.3 ± 214.4 µg/mL (TMP and SDZ). The respective t<sub>max</sub> (time to reach C<sub>max</sub>) values were 20 ± 7.8 and 26.4 ± 7.2 min. The initial synovial fluid concentrations were high but decreased quickly. No horse had synovial concentrations of trimethoprim-sulphadiazine above the MIC at 12 h. Severe vasculitis and pain shortly after IVRLP, lasting up to one week post-injection, occurred in five out of 10 horses. In conclusion, IVRLP with trimethoprim-sulphadiazine cannot be recommended due to the low concentrations of synovial fluid over time and the frequent severe adverse effects causing pain and discomfort in treated horses. Thus, in cases of septic synovitis with bacteria sensitive to trimethoprim-sulphadiazine, other routes of administration should be considered.https://www.mdpi.com/2076-2615/11/7/2085horsepharmacokineticsTMSregional limb perfusion |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Kajsa Gustafsson Amos J. Tatz Roee Dahan Wiessam Abu Ahmad Malka Britzi Gila A. Sutton Gal Kelmer |
spellingShingle |
Kajsa Gustafsson Amos J. Tatz Roee Dahan Wiessam Abu Ahmad Malka Britzi Gila A. Sutton Gal Kelmer Synovial Concentration of Trimethoprim-Sulphadiazine Following Regional Limb Perfusion in Standing Horses Animals horse pharmacokinetics TMS regional limb perfusion |
author_facet |
Kajsa Gustafsson Amos J. Tatz Roee Dahan Wiessam Abu Ahmad Malka Britzi Gila A. Sutton Gal Kelmer |
author_sort |
Kajsa Gustafsson |
title |
Synovial Concentration of Trimethoprim-Sulphadiazine Following Regional Limb Perfusion in Standing Horses |
title_short |
Synovial Concentration of Trimethoprim-Sulphadiazine Following Regional Limb Perfusion in Standing Horses |
title_full |
Synovial Concentration of Trimethoprim-Sulphadiazine Following Regional Limb Perfusion in Standing Horses |
title_fullStr |
Synovial Concentration of Trimethoprim-Sulphadiazine Following Regional Limb Perfusion in Standing Horses |
title_full_unstemmed |
Synovial Concentration of Trimethoprim-Sulphadiazine Following Regional Limb Perfusion in Standing Horses |
title_sort |
synovial concentration of trimethoprim-sulphadiazine following regional limb perfusion in standing horses |
publisher |
MDPI AG |
series |
Animals |
issn |
2076-2615 |
publishDate |
2021-07-01 |
description |
The aim of this study was to investigate the safety and pharmacokinetics of trimethoprim-sulphadiazine administered via intravenous regional limb perfusion (IVRLP) into the cephalic vein. According to the hypothesis, the drug could be administered without adverse effects and the synovial concentrations would remain above the minimum inhibitory concentration (MIC) for trimethoprim-sulphadiazine (0.5 and 9.5 µg/mL) for 24 h. Ten (<i>n</i> = 10) horses underwent cephalic vein IVRLP with an Esmarch tourniquet applied for 30 min. Four grams (4 g) of trimethoprim-sulphadiazine (TMP-SDZ) were diluted at 0.9% NaCl for a total volume of 100 mL. Synovial fluid and blood samples were obtained immediately before IVRLP and at 0.25, 0.5, 2, 6, 12 and 24 h after the initiation of IVRLP. Trimethoprim and sulphadiazine concentrations were determined using a method based on liquid chromatography/tandem mass spectrometry. The C<sub>max</sub> (peak drug concentration) values were 36 ± 31.1 and 275.3 ± 214.4 µg/mL (TMP and SDZ). The respective t<sub>max</sub> (time to reach C<sub>max</sub>) values were 20 ± 7.8 and 26.4 ± 7.2 min. The initial synovial fluid concentrations were high but decreased quickly. No horse had synovial concentrations of trimethoprim-sulphadiazine above the MIC at 12 h. Severe vasculitis and pain shortly after IVRLP, lasting up to one week post-injection, occurred in five out of 10 horses. In conclusion, IVRLP with trimethoprim-sulphadiazine cannot be recommended due to the low concentrations of synovial fluid over time and the frequent severe adverse effects causing pain and discomfort in treated horses. Thus, in cases of septic synovitis with bacteria sensitive to trimethoprim-sulphadiazine, other routes of administration should be considered. |
topic |
horse pharmacokinetics TMS regional limb perfusion |
url |
https://www.mdpi.com/2076-2615/11/7/2085 |
work_keys_str_mv |
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