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.

Antimicrobial disposition in pulmonary epithelial lining fluid of horses, Part III. Cefquinome

“…Sampling of PELF was performed at 1, 2, 4, 8 and 12 h after drug administration. The procedure for collection of PELF samples in horses has been described previously (Winther et al, 2010b). Recovery of cefquinome from the cotton swab was >90%.…”

Bronchopulmonary pharmacokinetics of (R)‐salbutamol and (S)‐salbutamol enantiomers in pulmonary epithelial lining fluid and lung tissue of horses

“…PELF sampling was adapted from similar techniques first used in human subjects and subsequently applied to equine studies . To obtain PELF samples, cotton tip swabs were attached to the distal end of a nasogastric tube, sheathed in PVC tubing (1.2 cm external diameter, 1.8 m length) and inserted via the nose and into the trachea until wedged in the airway.…”

Antimicrobial drug concentrations and sampling techniques in the equine lung

“…Tubes with absorbent disc/cotton swab Absorbent discs or cotton swabs have been used to sample bronchial secretions/ PELF in calves (Halstead et al, 1992;Friis, 1993;McKellar et al, 1999;Sarasola et al, 2002), pigs (Agerso and Friis, 1998) and in horses (Godber et al, 1995;Winther et al, 2010aWinther et al, , b, 2011Winther et al, , 2012. The technique has been applied to both conscious and anaesthetised animals as a blind placement of a guarding tube into the distal bronchi, until wedging, and then passing a sampling disc/cotton swab for 1-2 min before withdrawal.…”

“…However, very low oral bioavailability was found for the formulation used (6-17%), making PELF concentrations only clinically relevant for very susceptible pathogens. Sulfadiazine/trimethoprim measured by HPLC technique was studied after IV, intragastric and oral administration (Winther et al, 2010a). After oral administration, it was difficult to maintain clinically relevant drug concentrations of trimethoprim in PELF as only half of the total drug concentrations measured in plasma were found in PELF and these depleted rapidly.…”