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Pharmacokinetics and bioavailability of doxycycline in turkeys
Authors:MDF SANTOS  H VERMEERSCH  J P REMON  M SCHELKENS  P DE BACKER†  HJJ van  BREE‡R DUCATELLE§  F HAESEBROUCK§
Institution:Laboratory of Pharmaceutical Technology, Faculty of Pharmacy, University of Gent, Harelbekestraat 72, B-9000 Gent, Belgium.;Oropharma N.V., Dijkstraat 30, 9140 Temse, Belgium;Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, University of Gent, Salisburylaan 133, B-9820 Merelbeke, Belgium;Department of Medical Imaging, Faculty of Veterinary Medicine, University of Gent, Casinoplein 24, B-9000 Gent, Belgium;Department of Pathology, Bacteriology and Poultry Diseases. Faculty of Veterinary Medicine, University of Gent, Salisburylaan 133, B-9820 Merelbeke, Belgium
Abstract:The pharmacokinetic parameters of doxycycline (DOX) were determined in 3 day, 3-, 6- and 12-week-old fasted turkeys, after a single intravenous (i.v.) dose of 25 mg doxycycline. HCl/kg body weight. Doxycycline disposition fitted an open two-compartment model. The mean (± SD) elimination half-life was 10.6 ± 0.7, 10.8 ± 1.5, 7.9 ± 1.4 and 10.0 ± 0.9 h in 3 day, 3-, 6- and 12-week-old turkeys, respectively. Mean (± SD) total body clearance was 0.19 (± 0.01), 0.27 (± 0.03), 0.11 (± 0.03) and 0.06 (± 0.01) L/h.kg in 3 day, 3-, 6- and 12-week-old turkeys, respectively. The steady-state volume of distribution was 1.77 (± 0.2), 2.1 (± 0.2), 0.7 (± 0.4) and 0.5 (± 0.2) L/kg in turkeys of the above mentioned ages, respectively. The AUC value significantly increased with the age of the turkeys. An oral doxycycline solution at a single dose of 25 mg/kg of body weight was administered to 3 day, 3-, 6- and 12-week-old turkeys. The maximal plasma concentrations in fasted turkeys were 3.8, 5.6, 7.4 and 5.7 μg/mL, with t max values of 4.7, 1.5, 2.8 and 5.4 h, for the different ages, respectively. In fed turkeys the C max values were 2.5, 6.1, 4.8 and 3.0 μg/mL, with t max values of 4.2, 5.3, 4.5 and 7.5 h, respectively. The absolute bioavailability in fasted turkeys varied between 25.0 ± 9.0% (for 12-week-old birds) and 63.5 ± 7.1% (for 3-week-old birds). The relative bioavailability varied between 40.0 ± 13.0% (for 12-week-old birds) and 83.7 ± 14.3% (for 3-week-old birds).
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