TY - JOUR
T1 - Antimicrobial disposition in pulmonary epithelial lining fluid of horses
T2 - Part I. Sulfadiazine and trimethoprim
AU - Winther, Lotte
AU - Guardabassi, Luca
AU - Baptiste, Keith Edward
AU - Friis, Christian
PY - 2011/6
Y1 - 2011/6
N2 - 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 (25/5mg/kg) was administered intravenously, intragastric or per os to fed horses, and blood samples were collected before and 11 times, over 24h, 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.
AB - 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 (25/5mg/kg) was administered intravenously, intragastric or per os to fed horses, and blood samples were collected before and 11 times, over 24h, 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.
U2 - 10.1111/j.1365-2885.2010.01228.x
DO - 10.1111/j.1365-2885.2010.01228.x
M3 - Journal article
C2 - 20950347
SN - 0140-7783
VL - 34
SP - 277
EP - 284
JO - Journal of Veterinary Pharmacology and Therapeutics
JF - Journal of Veterinary Pharmacology and Therapeutics
IS - 3
ER -