Trimethoprim/sulfonamide combinations in the horse: a review.
Abstract: The indications for use, side-effects, and pharmacokinetic parameters of trimethoprim, sulfonamides and their combinations in the horse are reviewed. Trimethoprim/sulfonamide (TMPS) combinations are used for the treatment of various diseases caused by gram-positive and gram-negative bacteria, including infections of the respiratory tract, urogenital tract, alimentary tract, skin joints and wounds. TMPS combinations can be administered orally, since absorption from the gastrointestinal tract is relatively good. However, peak serum concentrations can vary significantly between individual horses. Feed intake affects serum concentrations after oral administration. Concentrations of non-bound trimethoprim (TMP) and sulfadiazine (SDZ) in synovial fluid and peritoneal fluid are equal to serum concentrations after intravenous (i.v.) administration, and high concentrations are found in urine. Concentrations of TMP and sulfamethoxazole (SMX) in cerebrospinal fluid after i.v. administration exceed the minimum inhibitory concentration for common equine pathogens. The volume of distribution is 1.5-2.7 l/kg for TMP and 0.3-0.7 l/kg for various sulfonamides. The plasma half-life of TMP is 1.9-4.3 h, whereas the plasma half-lives of the different sulfonamides vary between 2.7 and 14.0 h. About 50% of total TMP is bound to plasma proteins. The binding of sulfadoxine to plasma proteins depends on total plasma concentration and varies between 14% and 72%. The binding of other sulfonamides to plasma proteins may range from 33% for sulfaphenazole (SPZ) to 93% for sulfadimethoxine (SDM). Sulfonamides are metabolized by acetylation of the para-amino (N4) group and by hydroxylation of the methyl group and the pyrimidine ring. The metabolic pathways of TMP in the horse are not fully known. Bacterial resistance to TMPS combinations is still relatively low. The sensitivity of different micro-organisms may vary with the relative activity of the sulfonamide used in the combination. The advised oral and i.v. dose rate is 15-30 mg/kg (in a 1:5 TMP/S ratio) with a dose interval of 12 h. The acute toxicity of TMPS is low, but there have been several reports of death after i.v. administration, probably due to vagal stimulation and subsequent bradycardia and vasodilatation caused by the pharmaceutical formulation (excipients, solvents) used. Future research should concentrate on establishing the optimum pyrimidine/sulfonamide combination and its dosing regimen for antimicrobial therapy in horses.
Publication Date: 1994-02-01 PubMed ID: 8196097DOI: 10.1111/j.1365-2885.1994.tb00524.xGoogle Scholar: Lookup
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Summary
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This article reviews the usage, side effects, and pharmacokinetics of trimethoprim/sulfonamide combinations in horses, often employed to treat various bacterial diseases. However, this treatment’s effectiveness can vary due to absorption rates, individual horses’ metabolic rates and feed intake. Additionally, potential bacterial resistance and possible toxicity highlight the need for further research to determine optimal dosing regimens.
Indications and Administration of Trimethoprim/Sulfonamide Combinations
- Trimethoprim/sulfonamide (TMPS) combinations are commonly administered orally to horses to treat a range of diseases caused by both gram-positive and gram-negative bacteria.
- These diseases can include infections of the respiratory, urogenital, alimentary tracts, skin joints, and wounds.
- The absorption rate of these combinations through the horses’ gastrointestinal tract is relatively good, but peak serum concentrations can significantly vary between individual horses.
- Feed intake is one of the factors affecting the serum concentrations after oral administration of this drug combination.
Pharmacokinetics of Trimethoprim/Sulfonamide Combinations
- High concentrations of trimethoprim (TMP) and sulfadiazine (SDZ) can be found in synovial fluid, peritoneal fluid, and urine after these drugs are given intravenously.
- The volume of distribution is considerably different between TMP and different sulfonamides, with TMP ranging from 1.5-2.7 l/kg and sulfonamides between 0.3-0.7 l/kg.
- The plasma half-life, or time it takes for the concentration of the drug to reduce by half, also differs between TMP and various sulfonamides.
- About 50% of total TMP binds to plasma proteins, and the binding of sulfadoxine to plasma proteins can range from 14% to 72% depending on total plasma concentration.
- The metabolic pathways of TMP in horses are still not fully understood.
Resistance and Side Effects of Trimethoprim/Sulfonamide Combinations
- While bacterial resistance to TMPS combinations remains relatively low, the sensitivity can fluctuate according to the relative activity of the sulfonamide used in the combination.
- The acute toxicity of TMPS is low, but there have been several reports of fatal incidents after intravenous administration, likely due to vagal stimulation and subsequent bradycardia and vasodilatation due to the pharmaceutical formulation used.
- This suggests that improvements can be made to pharmaceutical formulations to increase their safety profile.
- Further research is needed to determine the optimal pyrimidine/sulfonamide combination and its dosing regimen for antimicrobial therapy in horses.
Cite This Article
APA
Van Duijkeren E, Vulto AG, Van Miert AS.
(1994).
Trimethoprim/sulfonamide combinations in the horse: a review.
J Vet Pharmacol Ther, 17(1), 64-73.
https://doi.org/10.1111/j.1365-2885.1994.tb00524.x Publication
Researcher Affiliations
- Department of Large Animal Medicine and Nutrition, Faculty of Veterinary Medicine, University of Utrecht, The Netherlands.
MeSH Terms
- Animals
- Bacterial Infections / drug therapy
- Bacterial Infections / veterinary
- Drug Therapy, Combination
- Horse Diseases / drug therapy
- Horse Diseases / microbiology
- Horses / metabolism
- Sulfonamides / pharmacokinetics
- Sulfonamides / therapeutic use
- Trimethoprim / pharmacokinetics
- Trimethoprim / therapeutic use
References
This article includes 72 references
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