Antimicrobial disposition in pulmonary epithelial lining fluid of horses. Part I. Sulfadiazine and trimethoprim.
Abstract: Sulfadiazine (SDZ) and trimethoprim (TMP) concentrations were examined in plasma and pulmonary epithelial lining fluid (PELF), following intravenous and oral administration and compared to minimum inhibitory concentrations (MICs) of common bacterial isolates from equine lower airway infections. SDZ/TMP (25/5 mg/kg) was administered intravenously, intragastric or per os to fed horses, and blood samples were collected before and 11 times, over 24 h, after administration. PELF samples were collected via a tampon device four times after drug administration and analysed for drug concentrations. Additionally, MICs of SDZ and TMP alone and in combination were determined in a selection of clinical respiratory isolates. Bioavailability was 74% for SDZ and 46% for TMP after paste administration in fed horses. The degree of penetration of SDZ and TMP into PELF, as described by AUC(PELF) /AUC(plasma) ratios, was 0.68 and 0.72, respectively, after intravenous administration. After oral administration, the degree of penetration for SDZ and TMP was 0.92 and 0.46, respectively. MIC measurements using SDZ/TMP ratios of 5:1 and 10:1 did not affect the interpretation of the results. The results indicate that clinically relevant drug concentrations of mainly TMP are difficult to maintain in PELF, especially after oral administration of SDZ/TMP.
© 2010 Blackwell Publishing Ltd.
Publication Date: 2010-08-24 PubMed ID: 20950347DOI: 10.1111/j.1365-2885.2010.01228.xGoogle Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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The research article investigates the concentrations of Sulfadiazine and trimethoprim antibiotics in the blood and lung fluid of horses, following different methods of administration, in order to determine their effectiveness in treating bacterial infections of the equine lower airways.
Research Methodology
- The dosages of Sulfadiazine (SDZ) and trimethoprim (TMP) were administered to the horses either intravenously (IV), intragastrically (IG), or orally, with a dosage of 25/5 mg/kg
- Samples of blood and pulmonary epithelial lining fluid (PELF) were collected over a 24-hour period after antibiotic administration. The blood was collected 11 times, while PELF samples were obtained four times.
- The collected samples were analyzed to ascertain the drug concentrations in them.
Results and Findings
- The bioavailability, or proportion of the drug that enters the circulation and exhibits an active effect, of SDZ was 74% and of TMP was 46% after paste administration in fed horses.
- Drug penetration into PELF was assessed by comparing the area under the curve (AUC) ratios of drug concentration over time in PELF and plasma. For SDZ, the AUC ratio was 0.68, and for TMP, it was 0.72 after an IV administration.
- After oral administration, the AUC ratio for SDZ was 0.92 and for TMP was 0.46, indicating a reduced penetration into PELF for TMP.
- Minimum inhibitory concentrations (MICs), or the least concentration of an antibiotic required to inhibit the growth of a bacteria, were also tested for SDZ and TMP alone and in combination across a selection of clinical respiratory isolates.
- Using different SDZ/TMP ratios did not affect the interpretation of the results.
Conclusion
- The findings suggest that maintaining clinically effective drug concentrations of TMP in the PELF is challenging, particularly when the SDZ/TMP is administered orally. This could limit the efficacy of these antibiotics in the treatment of lower airway infections in equine.
Cite This Article
APA
Winther L, Guardabassi L, Baptiste KE, Friis C.
(2010).
Antimicrobial disposition in pulmonary epithelial lining fluid of horses. Part I. Sulfadiazine and trimethoprim.
J Vet Pharmacol Ther, 34(3), 277-284.
https://doi.org/10.1111/j.1365-2885.2010.01228.x Publication
Researcher Affiliations
- Department of Large Animal Sciences, Faculty of Life Sciences, University of Copenhagen, Taastrup, Denmark. low@dkma.dk
MeSH Terms
- Administration, Oral
- Animals
- Anti-Bacterial Agents / administration & dosage
- Anti-Bacterial Agents / pharmacokinetics
- Biological Availability
- Chromatography, High Pressure Liquid / veterinary
- Drug Administration Schedule / veterinary
- Escherichia coli / drug effects
- Female
- Horses / metabolism
- Injections, Intravenous / veterinary
- Microbial Sensitivity Tests / veterinary
- Respiratory Mucosa / metabolism
- Staphylococcus aureus / drug effects
- Streptococcus equi / drug effects
- Sulfadiazine / administration & dosage
- Sulfadiazine / pharmacokinetics
- Trimethoprim / administration & dosage
- Trimethoprim / pharmacokinetics
Citations
This article has been cited 5 times.- Koutsoumanis K, Allende A, Alvarez-Ordóñez A, Bolton D, Bover-Cid S, Chemaly M, Davies R, De Cesare A, Herman L, Hilbert F, Lindqvist R, Nauta M, Ru G, Simmons M, Skandamis P, Suffredini E, Andersson DI, Bampidis V, Bengtsson-Palme J, Bouchard D, Ferran A, Kouba M, López Puente S, López-Alonso M, Nielsen SS, Pechová A, Petkova M, Girault S, Broglia A, Guerra B, Innocenti ML, Liébana E, López-Gálvez G, Manini P, Stella P, Peixe L. Maximum levels of cross-contamination for 24 antimicrobial active substances in non-target feed. Part 11: Sulfonamides. EFSA J 2021 Oct;19(10):e06863.
- 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).
- Jacobson GA, Raidal S, Robson K, Narkowicz CK, Nichols DS, Haydn Walters E. Bronchopulmonary pharmacokinetics of (R)-salbutamol and (S)-salbutamol enantiomers in pulmonary epithelial lining fluid and lung tissue of horses. Br J Clin Pharmacol 2017 Jul;83(7):1436-1445.
- Rodvold KA, George JM, Yoo L. Penetration of anti-infective agents into pulmonary epithelial lining fluid: focus on antibacterial agents. Clin Pharmacokinet 2011 Oct;50(10):637-64.
- Chen CL, Chen WP, Chang FY, Yu CM, Siu LK, Yang YS, Lin JC, Wang CH. Comparison of clinical and safety outcomes in patients with Stenotrophomonas maltophilia bacteremia: a trimethoprim/sulfamethoxazole versus levofloxacin monotherapy. Infection 2026 Feb;54(1):459-471.
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