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Canadian journal of veterinary research = Revue canadienne de recherche veterinaire1990; 54(2); 215-222;

Concentrations of trimethoprim and sulfamethoxazole in cerebrospinal fluid and serum in mares with and without a dimethyl sulfoxide pretreatment.

Abstract: Each of seven mares was given an intravenous (IV) injection of 40% dimethyl sulfoxide (DMSO) at a dosage of 1 g/kg, over 35 min, immediately followed by a single IV injection of a trimethoprim (TMP) and sulfamethoxazole (SMZ) combination (SMZ 83%, TMP 17%) at a combined dosage of 44 mg/kg (7.48 mg/kg TMP; 36.52 mg/kg SMZ). Each horse served as its own control and was alternately treated with an identical dose of TMP-SMZ treatment alone at least seven days following or preceding the DMSO and TMP-SMZ treatment. Serum and cerebrospinal fluid (CSF) concentrations of TMP and SMZ were measured over a six hour period. Dimethyl sulfoxide treatment caused no significant difference in the mean serum concentration of SMZ or in the mean CSF concentrations of TMP or SMZ. The mean serum concentration of TMP was significantly (p less than 0.05) increased at the two, four and six hour sampling time in the mares receiving pretreatment with DMSO. The clearance of TMP was also significantly (p less than 0.05) decreased from 675 mL/h/kg to 327 mL/h/kg by DMSO administration. Concentrations of TMP and SMZ in the CSF in both treatment groups exceeded the minimum inhibitory concentrations for many common bacterial pathogens of equine origin. In addition, CSF concentration of TMP exceeded the serum concentrations required for 50% inhibition of dihydrofolate reductases of protozoan origin. Serum TMP and SMZ concentration were similar to those reported to be effective against Toxoplasma gondii in in vitro studies on the killing or inhibition of the organism.
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Publication Date: 1990-04-01 PubMed ID: 2357657PubMed Central: PMC1255637
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  • Comparative Study
  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research investigated the effect of pretreatment with dimethyl sulfoxide (DMSO) on the concentrations of trimethoprim (TMP) and sulfamethoxazole (SMZ) in horses’ cerebrospinal fluid and blood serum. The results suggest that DMSO does not significantly alter the mean concentration of SMZ in the serum or the mean concentrations of TMP or SMZ in the cerebrospinal fluid, but it significantly increases TMP concentration in the serum while reducing its clearance rate.

Study Methods

  • The research used seven mares as subjects. The mares received intra-venous injection of 40% DMSO (1 gram per kilogram body weight) over 35 minutes. This was followed by an intra-venous injection of a TMP-SMZ combination.
  • An identical dose was also given to each of the horses without any pretreatment. This served as a control to allow comparison with the effects of the DMSO pretreatment.
  • Researchers evaluated the concentrations of TMP and SMZ in the serum and cerebrospinal fluid at various intervals over a six-hour period after the injections.

Findings

  • Dimethyl sulfoxide did not significantly alter the mean serum concentration of sulfamethoxazole or the mean cerebrospinal fluid concentrations of trimethoprim or sulfamethoxazole.
  • The mean serum concentration of trimethoprim was significantly increased in the horses that had received the pretreatment with DMSO.
  • The clearance of trimethoprim was significantly decreased by the administration of DMSO.
  • Concentrations of TMP and SMZ in the cerebrospinal fluid in both treatment groups exceeded the minimum inhibitory concentrations against common bacterial pathogens of equine origin. Hence, both treatments were effective against these pathogens.

Implications

  • While DMSO pretreatment did not significantly affect SMZ concentration in horses, it did increase TMP concentration in the serum and decreased its clearance rate. This indicates that DMSO could potentially be used to enhance the effectiveness of TMP against bacterial infections in horses.
  • The concentrations of TMP and SMZ in the cerebrospinal fluid after both treatments were sufficient to inhibit many common bacterial pathogens of equine origin, indicating effectiveness of the treatments.

Cite This Article

APA
Green SL, Mayhew IG, Brown MP, Gronwall RR, Montieth G. (1990). Concentrations of trimethoprim and sulfamethoxazole in cerebrospinal fluid and serum in mares with and without a dimethyl sulfoxide pretreatment. Can J Vet Res, 54(2), 215-222.

Publication

Canadian journal of veterinary research = Revue canadienne de recherche veterinaire
ISSN: 0830-9000
NlmUniqueID: 8607793
Country: Canada
Language: English
Volume: 54
Issue: 2
Pages: 215-222

Researcher Affiliations

Green, S L
  • Department of Large Animal Clinical Sciences, College of Veterinary Medicine, University of Florida, Gainesville 32610-0126.
Mayhew, I G
    Brown, M P
      Gronwall, R R
        Montieth, G

          MeSH Terms

          • Animals
          • Dimethyl Sulfoxide / pharmacology
          • Erythrocyte Count / veterinary
          • Female
          • Horses / blood
          • Horses / cerebrospinal fluid
          • Horses / metabolism
          • Injections, Intravenous / veterinary
          • Leukocyte Count / veterinary
          • Sulfamethoxazole / blood
          • Sulfamethoxazole / cerebrospinal fluid
          • Trimethoprim / blood
          • Trimethoprim / cerebrospinal fluid
          • Trimethoprim, Sulfamethoxazole Drug Combination / administration & dosage
          • Trimethoprim, Sulfamethoxazole Drug Combination / pharmacokinetics

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          Citations

          This article has been cited 1 times.
          1. Reed SM, Furr M, Howe DK, Johnson AL, MacKay RJ, Morrow JK, Pusterla N, Witonsky S. Equine Protozoal Myeloencephalitis: An Updated Consensus Statement with a Focus on Parasite Biology, Diagnosis, Treatment, and Prevention. J Vet Intern Med 2016 Mar-Apr;30(2):491-502.
            doi: 10.1111/jvim.13834pubmed: 26857902google scholar: lookup
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