Pharmacotherapeutic group: Tetracyclines.
ATCvet code: QJ01AA02
Pharmacodynamic properties
Doxycycline belongs to the group of the tetracycline antibiotics. These antibiotics have a broad spectrum of antimicrobial activity, sharing the same basic structure of polycyclic naphthacenecarboxamide.
Doxycycline is primarily a bacteriostatic drug. It exerts its action by inhibiting the protein synthesis of the bacterial cell. Inhibition of bacterial protein synthesis results in disturbance of all functions necessary for the life of bacteria. In particular, cell-division and the formation of the cell wall are impaired.
Doxycycline is a broad spectrum antibiotic.
The MIC90 of doxycycline against Mycoplasma gallisepticum strains isolated in France, Germany and Hungary (2003-2009) was reported 0.5 µg/ml. The resistance rate of M. gallisepticum isolates against doxycycline is low.
Four resistance mechanisms acquired by micro-organisms against tetracyclines in general have been reported: decreased accumulation of tetracyclines (decreased permeability of the bacterial cell wall and active efflux), protein protection of the bacterial ribosome, enzymatic inactivation of the antibiotic and rRNA mutations (preventing the tetracycline binding to ribosome). Tetracycline resistance is usually acquired by means of plasmids or other mobile elements (e.g. conjugative transposones). Cross-resistance between tetracyclines has also been described. Due to the greater liposolubility and greater facility to pass through cell membranes (in comparison to tetracycline), doxycycline retains a certain degree of efficacy against micro-organisms with acquired resistance to tetracyclines.
Pharmacokinetic properties
In general, doxycycline is quite rapidly and extensively absorbed from the gastrointestinal tract, widely distributed in the organism, not metabolised to any significant extent and excreted mostly via the faeces.
The pharmacokinetics of doxycycline after single oral administration to turkeys is characterised by a quite rapid and substantial absorption from the gastrointestinal tract providing peak plasma concentrations between 1.5-7.5 hours depending on age and the presence of food. The drug is widely distributed in the organism with Vd values close to or greater than 1, and exhibits an elimination half-life in turkeys of 7.9-10.8 hours. The protein binding ratio at therapeutic plasma concentrations is in the range of 70-85%. The bioavailability in turkeys may vary between 25-64%, also depending on age and feeding. The presence of food in the gastrointestinal tract determines a lower bioavailability compared to that obtained in the fasted state.
After continuous in-water administration of the product at dosages of 25 mg doxycycline/kg in turkeys for 5 days the average plasma concentrations over the whole treatment period were reported 2.24±1.02 µg/ml in turkeys. PK/PD analysis of ƒAUC/MIC90 data resulted in > 24 hours values that meet the requirements for tetracyclines.