Pharmacokinetics and therapeutic potential for repeated oral doses of trimethoprim/sulphachlorpyridazine in horses.
Abstract: The pharmacokinetic parameters of a powder formulation of trimethoprim/sulphachlorpyridazine were studied in eight healthy horses which received 5 mg/kg trimethoprim and 25 mg/kg sulphachlorpyridazine 12-hourly with concentrate for five days. The intake of the medicated concentrate by the horses was variable during the first two days, but after they became accustomed to the taste the intake by all the horses during the last three days was good. Faecal samples taken before and on the last day of the drug administrations were negative when cultured for salmonella. Compared with the results of a previous single-dose experiment, higher plasma concentrations and a higher area under the curve for both the drugs were observed. The repeated doses provided plasma concentrations above the minimal inhibitory concentration for Streptococcus zooepidemicus, S equi, Actinobacillus equuli and Rhodococcus equi isolated from the respiratory tract of horses. Synergism between the two drugs occurred at different drug concentration ratios with different bacterial species.
Publication Date: 1995-11-04 PubMed ID: 8578661DOI: 10.1136/vr.137.19.483Google Scholar: Lookup
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- Clinical Trial
- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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This study examines how a powder formulation of two drugs, trimethoprim and sulphachlorpyridazine, behaves in the body of horses when given repeatedly, and how effective these doses are in treating certain bacterial infections.
Research Methodology
- The research was conducted on eight healthy horses, where a powdered formulation of two drugs, trimethoprim and sulphachlorpyridazine, was administered.
- Each horse received these drugs 12-hourly mixed with their feed for a duration of five days. The dosage given was 5 mg/kg trimethoprim and 25 mg/kg sulphachlorpyridazine.
- At first, the intake of the medicated feed was very variable, primarily because the horses needed to adjust to the taste. However, after a few days, all the horses started to consume the medicine-filled feed regularly.
- Before the start of this medication schedule, and at the end, faecal samples were collected from the horses and analyzed for the presence of salmonella bacteria. All samples were found to be negative for this pathogen.
Observations and Findings
- When the results from this experimental setting were compared with a previous single-dose administration of these drugs, it was noticed that the repeated doses led to higher plasma concentrations of the drugs. Furthermore, these drugs stayed longer in the system, as suggested by the higher area under the curve.
- The drug concentrations achieved in the blood were found to be above the minimum levels required to inhibit the growth of certain bacteria that can lead to respiratory infections in horses. These include Streptococcus zooepidemicus, Streptococcus equi, Actinobacillus equuli, and Rhodococcus equi.
- A synergistic relationship was also seen between the two drugs, meaning their combined effect was greater than their individual effects when administered separately. However, the degree and nature of this synergy varied depending on the species of the bacteria.
Conclusion
- This study suggests that the combined use of trimethoprim and sulphachlorpyridazine has therapeutic potential in treating bacterial infections in horses, particularly respiratory ones. The fact that repeated doses resulted in sufficiently high and enduring drug concentrations in the body, and were also effective against various microbial pathogens, further support this finding.
- However, it is important to note that horses might initially refuse the medicated feed due to the change in taste. Therefore, care should be taken to ensure proper intake of the medicaments during the initial days of this treatment regimen.
Cite This Article
APA
van Duijkeren E, Sloet van Oldruitenborgh-Oosterbaan MM, Vulto AG, Kessels BG, van Miert AS, Breukink HJ.
(1995).
Pharmacokinetics and therapeutic potential for repeated oral doses of trimethoprim/sulphachlorpyridazine in horses.
Vet Rec, 137(19), 483-486.
https://doi.org/10.1136/vr.137.19.483 Publication
Researcher Affiliations
- Department of Large Animal Medicine and Nutrition, Veterinary Hospital Pharmacy, Utrecht, The Netherlands.
MeSH Terms
- Administration, Oral
- Animals
- Anti-Bacterial Agents / pharmacokinetics
- Anti-Bacterial Agents / pharmacology
- Anti-Bacterial Agents / therapeutic use
- Bacteria / drug effects
- Drug Combinations
- Drug Synergism
- Female
- Horses / metabolism
- Horses / microbiology
- Male
- Microbial Sensitivity Tests / veterinary
- Respiratory System / microbiology
- Sulfachlorpyridazine / pharmacokinetics
- Sulfachlorpyridazine / pharmacology
- Sulfachlorpyridazine / therapeutic use
- Trimethoprim / pharmacokinetics
- Trimethoprim / pharmacology
- Trimethoprim / therapeutic use
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