Pharmacotherapeutic group: antibacterials for systemic use; macrolides, tilmicosin
ATCVet code: QJ01FA91
Pharmacodynamic properties
Tilmicosin is a mainly bactericidal semi-synthetic antibiotic of the macrolide group. It is believed to affect the bacterial protein synthesis in vitro and in vivo, without affecting the nucleic acid synthesis. It is mostly bacteriostatic. It has a bactericidal effect on Pasteurella spp.
Tilmicosin has a wide spectrum of activity against Gram-positive organisms is particularily active against Pasteurella, Actinobacillus (Haemophilus) and Mycoplasma organisms of bovine, porcine and avian origin Tilmicosin has some activity against certain Gram-negative micro-organisms.
Macrolides inhibit protein synthesis by reversibly binding to the 50S ribosomal subunit. Bacterial growth is inhibited by induction of the separation of peptidyl transfer RNA from the ribosome during the elongation phase.
Ribosomal methylase, encoded by the erm gene, can precipitate resistance to macrolides by alteration of the ribosomal binding site.
The gene that encodes for an efflux mechanism, mef, also brings about a moderate degree of resistance.
Resistance is also brought about by an efflux pump that actively rids the cells of the macrolide. This efflux pump is chromosomally mediated by genes referred to as acrAB genes. Resistance of Pseudomonas species and other Gram negative bacteria, enterococci and staphylococci may be precipitated by chromosomally controlled alteration of permeability or uptake of the drug.
Pharmacokinetic properties
Pigs:
Absorption: When administered to pigs via the oral route at a dose of 400 mg tilmicosin/kg feed (equivalent to approximately 21.3 mg tilmicosin/kg bodyweight/day), tilmicosin moves rapidly out of the serum into areas of low pH. The highest concentration in the serum (0.23 ±0.08 µg/ml) was recorded on day 10 of medication, but concentrations above the limit of quantification (0.10 µg/ml) were not found in 3 out of 20 animals examined. Lung concentrations increased rapidly between days 2 and 4 but no significant changes were obtained following four days of dosing. The maximum concentration in lung tissue (2.59±1.01 µg/ml) was recorded on day 10 of medication.
When administered at a dose of 200 mg tilmicosin/kg feed (equivalent to approximately 11.0 mg/kg/day), plasma concentrations above the limit of quantification (0.10 µg/ml) were found in 3 out of 20 animals examined. Quantifiable levels of tilmicosin were found in lung tissue with the maximum concentration (1.43±1.13 µg/ml) being recorded on day 10 of medication.
Distribution: Following oral administration, tilmicosin is distributed throughout the body with especially high levels found in the lung and in lung tissue macrophages. It is also distributed in the liver and kidney tissues.
Rabbits:
Absorption: When administered orally to rabbits at a dose of 12 mg tilmicosin/kg b.w. as a single dose there is a quick absorption. Maximum concentrations were reached in 30 minutes, being the Cmax obtained of 0.35 µg/ml. Tilmicosin plasma concentrations decreased to 0.1 µg/ml within 2 hours and to 0.02 µg/ml after 8 hours. The elimination half-life was 22 hours.
Distribution: Following oral administration, tilmicosin is distributed throughout the body with especially high levels found in lungs. After 5 days of treatment with medicated feed at a dosage of 200 ppm of product, tilmicosin concentrations in lung tissues were of 192 ± 103 µg/g.
Applicable to both species:
Biotransformation: Several metabolites are formed, the predominant one being identified as T1. However the bulk of tilmicosin is excreted unchanged.
Elimination: Following oral administration, tilmicosin is excreted mainly via the bile into the faeces but a small proportion is excreted via the urine.