Synovial Concentration of Trimethoprim-Sulphadiazine Following Regional Limb Perfusion in Standing Horses.
Abstract: 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 ( = 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 (peak drug concentration) values were 36 ± 31.1 and 275.3 ± 214.4 µg/mL (TMP and SDZ). The respective t (time to reach C) 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.
Publication Date: 2021-07-13 PubMed ID: 34359213PubMed Central: PMC8300224DOI: 10.3390/ani11072085Google Scholar: Lookup
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Summary
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The research study investigates administering trimethoprim-sulphadiazine via the intravenous regional limb perfusion method in horses to measure its safety and effectiveness. Despite initial high levels of the drug in synovial fluid, concentration decreased quickly and adverse side effects were observed, leading the researchers to recommend alternative administration routes when treating septic synovitis in horses.
Objective of the Study
- The main objective of this research was to assess the safety and efficacy of administering trimethoprim-sulphadiazine via intravenous regional limb perfusion (IVRLP) in horses. The researchers hypothesised that the drug could be administered in this way without any adverse effects and that the drug concentration in the synovial fluid would exceed the minimum inhibitory concentration (MIC) for at least 24 hours.
Methodology
- The study involved ten horses which underwent cephalic vein IVRLP. A tool called an Esmarch tourniquet was applied for 30 minutes.
- Four grams of trimethoprim-sulphadiazine were diluted with 0.9% NaCl saline solution for a total volume of 100 millilitres.
- Synovial fluid and blood samples were taken before initiating IVRLP and at various intervals post-administration of the drug (0.25, 0.5, 2, 6, 12, and 24 hours).
- The concentrations of trimethoprim and sulphadiazine, the two active ingredients of the drug, were determined through a liquid chromatography/tandem mass spectrometry method.
Findings
- The peak drug concentration values were decent initially both for trimethoprim and sulphadiazine, but the concentrations in the synovial fluid decreased rapidly over time.
- No horse had synovial concentrations of trimethoprim-sulphadiazine above the minimum inhibitory concentration at 12 hours post administration.
- Adverse effects such as severe vasculitis (inflammation of the blood vessels) and pain were observed in half of the horses shortly after IVRLP, which lasted up to one week post-injection.
Conclusion
- The study concluded that the administration of the antibiotic combination trimethoprim-sulphadiazine through IVRLP is not recommended due to the low drug concentrations in synovial fluid over time and the frequent severe adverse effects causing pain and discomfort in the treated horses.
- Alternative routes of administration should be explored for treating conditions like septic synovitis in horses with bacteria that are sensitive to the drug.
Cite This Article
APA
Gustafsson K, Tatz AJ, Dahan R, Abu Ahmad W, Britzi M, Sutton GA, Kelmer G.
(2021).
Synovial Concentration of Trimethoprim-Sulphadiazine Following Regional Limb Perfusion in Standing Horses.
Animals (Basel), 11(7), 2085.
https://doi.org/10.3390/ani11072085 Publication
Researcher Affiliations
- Department 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, Israel.
- Department 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, Israel.
- Department 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, Israel.
- Faculty of Medicine, Hebrew University-Hadassah Braun School of Public Health and Community Medicine, Jerusalem 9112102, Israel.
- National Residue Control Laboratory, Kimron Veterinary Institute, Bet Dagan 50250, Israel.
- Department 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, Israel.
- Department 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, Israel.
Conflict of Interest Statement
The authors declare no conflict of interest related to this report.
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Citations
This article has been cited 2 times.- Redding LE, Elzer EJ, Ortved KF. Effects of regional limb perfusion technique on concentrations of antibiotic achieved at the target site: A meta-analysis. PLoS One 2022;17(4):e0265971.
- Mita H, Kuroda T, Niwa H, Tamura N, Fukuda K, Ohta M. Incidence of surgical site infection after internal fixation of the first phalangeal bone and the third metacarpal/metatarsal bone fractures in Thoroughbred racehorses. J Equine Sci 2023 Sep;34(3):61-66.
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