Pharmacokinetics of ceftazidime after regional limb perfusion in standing horses.
Abstract: To determine the metacarpophalangeal joint fluid concentrations of ceftazidime administered via regional limb perfusion (RLP). Methods: Eight healthy horses. Methods: RLP was performed by injecting 2 g of ceftazidime and 60 mL of perfusate volume in the cephalic vein of standing, sedated horses. Serum and synovial fluid from the metacarpophalangeal joint were collected before perfusion and at 0.5, 2, 6, 12, 24 hours postperfusion. Ceftazidime concentrations were measured via liquid chromatography. Maximal concentration (C ), area under the curve (AUC), half-life of the drug (T ½), and the timing of C (T ) were determined to assess ceftazidime as a candidate drug for RLP. Continuous parameters were compared with the Mann-Whitney U test. P value ≤ .05 was considered statistically significant. Results: The C of ceftazidime in synovial fluid (235 µg/mL) was 15 times higher than the minimal inhibitory concentration (MIC) for most bacteria involved in orthopedic infections, including resistant pathogens such as Pseudomonas aeruginosa (MIC = 16 µg/mL). However, synovial concentrations decreased quickly and remained above the MIC in only 1 horse by 6 hours postperfusion. Conclusions: RLP generated high synovial fluid concentrations of ceftazidime in the distal limb, but these concentrations decreased rapidly below the deliberately high MIC selected. Conclusions: Once daily RLP, as applied in our study, with 2 g ceftazidime in standing horses, cannot be recommended for use in a clinical setting.
© 2017 The American College of Veterinary Surgeons.
Publication Date: 2017-09-27 PubMed ID: 28952152DOI: 10.1111/vsu.12720Google Scholar: Lookup
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- Journal Article
- Antibiotics
- Biological Half-Life
- Clinical Findings
- Clinical Pathology
- Clinical Study
- Disease Treatment
- Drug
- Equine Health
- High-performance Liquid Chromatography (HPLC)
- Horses
- In Vivo
- Infection
- Metacarpophalangeal Joint
- Pathogens
- Pharmacokinetics
- Synovial Fluid
- Veterinary Medicine
- Veterinary Procedure
- Veterinary Research
Summary
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The research explores the concentration levels of a drug named ceftazidime in horse joints when administered through the procedure of regional limb perfusion (RLP). It concludes that although the drug concentration starts off high, it rapidly decreases to a level which is not therapeutic for treating bacterial infections in clinical settings.
Objective and Methods of the Study
- The drug ceftazidime was administered to eight healthy horses through a procedure known as regional limb perfusion (RLP), performed in their cephalic vein while sedated and standing.
- The process involved injecting 2g of ceftazidime and 60ml of perfusate volume into the horses and tracking the drug concentration in the horses’ metacarpophalangeal joint synovial fluid over time.
- Samples of serum and synovial fluid were collected before the perfusion process and at intervals of 0.5, 2, 6, 12, 24 hours postperfusion.
Measuring and Assessment Procedures
- The ceftazidime concentrations in the samples were measured via liquid chromatography.
- Parameters such as maximal concentration (C), area under the curve (AUC), the half-life of the drug (T ½), and the timing of C (T) were used to assess the suitability of ceftazidime as a drug for RLP.
- The comparisons of these continuous parameters were statistically analyzed using the Mann-Whitney U test, with a p-value ≤ .05 considered as statistically significant.
Findings and Conclusion
- The initial concentration of ceftazidime in the synovial fluid was found to be 15 times higher than the minimum inhibitory concentration (MIC) for most bacteria causing orthopedic infections, including resistant pathogens such as Pseudomonas aeruginosa.
- However, it was also observed that the synovial concentrations of the drug decreased quickly, remaining above the MIC in only a single horse, six hours after the perfusion.
- Because of the rapidly decreasing concentration of ceftazidime, the study concludes that once daily RLP with 2g ceftazidime is not recommended for clinical use in standing horses.
Cite This Article
APA
Oreff GL, Tatz AJ, Dahan R, Segev G, Haberman S, Britzi M, Kelmer G.
(2017).
Pharmacokinetics of ceftazidime after regional limb perfusion in standing horses.
Vet Surg, 46(8), 1120-1125.
https://doi.org/10.1111/vsu.12720 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, 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, 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, Israel.
- Department of Small 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, 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, Israel.
- National Residue Control Laboratory, Kimron Veterinary Institute, Bet Dagan, 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, Israel.
MeSH Terms
- Animals
- Anti-Bacterial Agents / blood
- Anti-Bacterial Agents / pharmacokinetics
- Ceftazidime / blood
- Ceftazidime / pharmacokinetics
- Female
- Forelimb / physiology
- Horses / physiology
- Injections, Intravenous / veterinary
- Joints / physiology
- Male
- Perfusion / veterinary
- Synovial Fluid / chemistry
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.
- Gustafsson K, Tatz AJ, Dahan R, Abu Ahmad W, Britzi M, Sutton GA, Kelmer G. Synovial Concentration of Trimethoprim-Sulphadiazine Following Regional Limb Perfusion in Standing Horses.. Animals (Basel) 2021 Jul 13;11(7).
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