Pharmacokinetics of oral doxycycline and concentrations in body fluids and bronchoalveolar cells of foals

Abstract

The objective of this study was to determine the disposition of orally administered doxycycline in foals. Six healthy 4- to 8-week-old foals were used. Doxycycline was administered to each foal via the intragastric (IG) route at dosages of 10 and 20 mg/kg, in a cross-over design. After the first 10 mg/kg dose, five additional doses were administered at 12-h intervals. A microbiological assay was used to measure doxycycline activity in serum, urine, peritoneal fluid, synovial fluid, cerebrospinal (CSF), pulmonary epithelial lining fluid (PELF), and bronchoalveolar (BAL) cells. Following administration at 10 mg/kg, mean+/-SD time to peak serum doxycycline activity (tmax) was 3.0+/-1.2 h, maximum serum activity (Cmax) was 2.54+/-0.27 microg/mL, and terminal half-life (t1/2) was 8.5+/-2.8 h. Administration at a dose of 20 mg/kg resulted in a significantly longer tmax (5.5+/-1.8 h) as well as a tendency toward higher Cmax (2.89+/-0.33 microg/mL) and longer t1/2 (11.9+/-2.6 h). After multiple IG doses, doxycycline activity in CSF was significantly lower than concurrent serum activity, whereas peritoneal fluid, synovial fluid, and BAL cell doxycycline activity was similar to concurrent serum activity. Doxycycline activity in urine and PELF was significantly higher than that found at other sites. Oral administration at a dosage of 10 mg/kg every 12 h would maintain serum, PELF, and BAL cell activity above the minimum inhibitory concentrations of Rhodococcus equi, beta-hemolytic streptococci, and other susceptible bacterial pathogens for the entire dosing interval.

Pharmacokinetics of an injectable long-acting formulation of doxycycline hyclate in dogs

“…For example Cp 0 with a 10 mg/kg dose was 23.54 ± 4.32 in this trial, and 11.77 ± 2.26 μg/mL in the referred study with a dose of 5  mg/kg;  AUC  was  109.66 ± 8.56  μg.h/mL  and  52.76 ± 15.34  μg.h/mL for obtained and reported results, respectively and elimination half-life was 0.09 h in both cases. The half-life value obtained for DOX-h-IV in this study falls within the range documented for other species varying from 4.2 h to 16.6 h [10,21-24]. However, no studies are available on the pharmacokinetics of neither the oral administration of the drug as tablets, nor the SC injection of a long-acting preparation, in dogs.…”

Pharmacokinetics of a peroral single dose of two long-acting formulations and an aqueous formulation of doxycycline hyclate in horses

“…The pharmacokinetics of an aqueous solution of Dox-h administered orally (PO) has been determined in adult horses [1,6,11,12] and in foals [2]. In these studies, Dox-h was administered either dissolved in water via nasogastric tube or as a top dressing at doses ranging from 3 mg/kg to 20 mg/kg every 12 (q12h) or every 24 hours (q24h).…”

“…On the other hand, Bryant et al [1] concluded that Dox-h at a dose of 10 mg/kg PO q12 h could be appropriate for treating infections caused by susceptible (MIC < 0.25 μg/ml) gram positive microorganisms. Yet, Davis et al [6] and Womble et al [2] consider that the therapeutic value of oral Dox-h in adult horses is limited due to its low bioavailability. Winther et al [12] reported an estimated oral bioavailability of Dox-h of 17% after intragastric administration and 6% after topdressing administration in non-fasted adult horses.…”

Disparities in TLR5 Expression and Responsiveness to Flagellin in Equine Neutrophils and Mononuclear Phagocytes

“…The bronchoalveolar lavage fluid was centrifuged at 400 3 g for 10 min, after which the cell pellet was washed twice with PBS at 20˚C and the cells collected as described previously (33). After washing, the cells were suspended in 10 ml PBS for viability assessment and cell counting in a hemacytometer.…”