Antimicrobial disposition in pulmonary epithelial lining fluid of horses. Part I. Sulfadiazine and trimethoprim.
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.
Department of Large Animal Sciences, Faculty of Life Sciences, University of Copenhagen, Taastrup, Denmark. low@dkma.dk
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Winther
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Guardabassi
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Baptiste
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Friis
D000284:Administration, Oral; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid / Q000662:veterinary; D004334:Drug Administration Schedule / Q000662:veterinary; D004926:Escherichia coli / Q000187:drug effects; D005260:Female; D006736:Horses / Q000378:metabolism*; D007275:Injections, Intravenous / Q000662:veterinary; D008826:Microbial Sensitivity Tests / Q000662:veterinary; D020545:Respiratory Mucosa / Q000378:metabolism*; D013211:Staphylococcus aureus / Q000187:drug effects; D018502:Streptococcus equi / Q000187:drug effects; D013411:Sulfadiazine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D014295:Trimethoprim / Q000008:administration & dosage / Q000493:pharmacokinetics*
D000900:Anti-Bacterial Agents; D013411:Sulfadiazine; D014295:Trimethoprim