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Pharmacological particulars
Pharmacotherapeutic group: Antibacterials for systemic use; Tetracyclines. ATCvet code: QJ01AA02.
Pharmacodynamic properties
Doxycycline is a broad-spectrum tetracycline-class antibiotic active against a large number of gram positive and gram negative bacteria including both aerobic and anaerobic species.
Doxycycline inhibits bacterial protein synthesis by binding to the 30-S ribosomal subunits. This interferes with binding of aminoacetyl-tRNA to the acceptor site on the mRNA ribosome complex and prevents coupling of amino acids to the elongating peptide chains; doxycycline has a predominantly bacteriostatic activity.
The penetration of doxycycline into the bacterial cell takes place by both active transport and passive diffusion.
The main mechanisms of acquired resistance to tetracycline class antibiotics include active efflux and ribosomal protection. A third mechanism is enzymatic degradation. The genes mediating resistance may be carried on plasmids or transposons, as for example, tet(M), tet(O), and tet(B) that can be found in both gram-positive and gram-negative organisms including clinical isolates.
Cross-resistance to other tetracyclines is common but depends on the mechanism conferring resistance. Due to the greater liposolubility and greater ability to pass through cell membranes (in comparison to tetracycline), doxycycline retains a certain degree of efficacy against microorganisms with acquired resistance to tetracyclines via efflux pumps. However, resistance mediated by ribosomal protection proteins confer cross-resistance to doxycycline.
The following MIC values for the targeted bacteria were collected between 2017 and 2018 as a part of ongoing European surveillance studies:
Bacterial pathogen
Origin (number of strains tested)
MIC50 (μg/ml)
MIC90 (μg/ml)
Bordatella bronchiseptica
Dog - respiratory tract (38)
0.12
0.5
Bordatella bronchiseptica
Cat - respiratory tract (11)
0.12
0.12
Pasteurella spp.
Dog - respiratory tract (27)
0.12
0.25
Pasteurella spp.
Cat - respiratory tract (77)
0.12
0.25
Antibiotic susceptibility data for Ehrlichia Canis are limited.
Pharmacokinetic properties
Absorption
After oral administration, the bioavailability of doxycycline is 45% in dogs and 48% in cats. Peak concentrations of 4.5 μg/ml (dogs) and 3.8 μg/ml (cats) are reached within 3 hours after oral administration, supporting that doxycycline is rapidly absorbed from the gastro-intestinal tract.
Distribution
Doxycycline is broadly distributed throughout the organism due to its physicochemical characteristics, as it is highly liposoluble. The distribution volume is 1.72 l/kg in dogs and 0.9 l/kg in cats, supporting that doxycycline diffuses from blood into tissues. Protein binding in dogs is reported as 91.75 % ± 0.63 and 91.4% in the literature. In cats a publication reports a protein binding of 98.35% (+/-0.24).
The tissue concentrations, with the exception of the skin, are generally higher than the plasma levels, including the excretion organs (liver, kidney and intestines) and for the lungs.
Elimination
After a single administration, the half-life elimination (TR1/2R) is 7.84 hours and 5.82 hours, in dogs and cats respectively. Excretion occurs in an unchanged active form (90%) via the faeces (approximately 75%), via the urine (approximately 25%) and less than 5% via the bile ducts.