Antimicrobial disposition in pulmonary epithelial lining fluid of horses, part II. Doxycycline.
Doxycycline concentrations, following two types of oral administration to horses, in pulmonary epithelial lining fluid (PELF) were examined and compared to plasma concentrations. The oral bioavailability was estimated from plasma concentrations achieved after an intravenous study in two horses. Doxycycline (10 mg/kg) was administered either intragastric or as topdressing to nonfasted horses. Blood samples were collected for drug analysis, before and 11 times after administration during 24 h. PELF samples were collected by a tampon device four times after drug administration and analysed for doxycycline concentrations. Another two horses received doxycycline intravenously at a dose of 3 mg/kg and plasma was taken 14 times during a 24- h period. The oral bioavailability of doxycycline was calculated to 17% after intragastric administration and 6% after topdressing administration in nonfasted horses. The degree of penetration of doxycycline into PELF, as described by AUC(PELF) /AUC(plasma) ratios, was 0.87 after intragastric administration. The results indicate that clinically relevant doxycycline concentrations are possible to maintain in PELF after intragastric administration. Furthermore, if bioavailability could be enhanced for per os administration, doxycycline might be a valuable drug for the treatment of lower airway infections in horses.
Department of Large Animal Sciences, Faculty of Life Sciences, University of Copenhagen, Taastrup, Denmark. low@dkma.dk
L
L
Winther
S
S
Honoré Hansen
K E
KE
Baptiste
C
C
Friis
D000284:Administration, Oral; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001682:Biological Availability; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid / Q000662:veterinary; D004318:Doxycycline / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004334:Drug Administration Schedule / Q000662:veterinary; D004926:Escherichia coli / Q000187:drug effects; D005260:Female; D006736:Horses; D007275:Injections, Intravenous / Q000662:veterinary; D013058:Mass Spectrometry / Q000662:veterinary; D008826:Microbial Sensitivity Tests / Q000662:veterinary; D010325:Pasteurella / Q000187:drug effects; D020545:Respiratory Mucosa / Q000378:metabolism*; D013211:Staphylococcus aureus / Q000187:drug effects; D018502:Streptococcus equi / Q000187:drug effects
D000900:Anti-Bacterial Agents; D004318:Doxycycline