ATC Vet Code: QJ01XQ01.
Pharmacotherapeutic group: antibacterials for systemic use, pleuromutilins.
Pharmacodynamic properties
Tiamulin is a bacteriostatic semi-synthetic antibiotic belonging to the pleuromutilin group of antibiotics and acts at the ribosomal level to inhibit bacterial protein synthesis.
Tiamulin has shown in-vitro activity against a wide range of bacteria including Brachyspira hyodysenteriae, Brachyspira pilosicoli, Lawsonia intracellularis and Mycoplasma spp.
Tiamulin is bacteriostatic at therapeutic concentrations and has been shown to act at the 70S ribosome level and the primary binding site is on the 50S subunit and possibly a secondary site where the 50S and 30S subunits join. It appears to inhibit microbial protein production by producing biochemical inactive initiation complexes, which prevent elongation of the polypeptide chain.
Mechanisms responsible for resistance development in Brachyspira spp to the pleuromutilin class of antibiotics are considered to be based on mutations at the ribosomal target site. Clinically relevant resistance to tiamulin requires combinations of mutations around the tiamulin binding site. Resistance to tiamulin may be associated with decreased susceptibility to other pleuromutilins.
Pharmacokinetic properties
Pigs:
Following oral administration, tiamulin hydrogen fumarate is rapidly absorbed from the gastrointestinal tract of pigs (85-90%) and appears in the blood within 30 minutes. 2-4 hours (tmax) after the oral administration of 10 mg tiamulin/kg BW in the form of an oral solution, a Cmax of 1 µg/ml was measured; an oral administration of 25 mg/kg gave a Cmax of 1.82 µg/ml.
There is very good distribution in the tissues with accumulation in lungs and in the colon. 30-50% of tiamulin is bound to serum proteins.
Tiamulin is rapidly metabolised in the liver (hydroxylation, de-alkalysation, hydrolysis). At least 16 biologically inactive metabolites have been identified. The excretion of tiamulin and its metabolites is through the bile and faeces (70-85%). The remainder is excreted through the urine (15-30%).
Chickens
Tiamulin is well absorbed in chickens (70-95%) after oral administration.
Tiamulin distributes widely through the body and has been shown to concentrate in the liver and kidney (sites of excretion) and in the lung (30 times serum level). Excretion is mainly via the bile (55-65%) and kidney (15-30%) as mainly microbiologically inactive metabolites and is quite rapid, 99% of the dose within 48 hours.
Turkeys
In turkeys serum levels of tiamulin are similar to chickens. In breeders on 0.025% tiamulin the average serum level was 0.36μg/ml (range 0.22-0.5μg/ml).
Rabbits
There are no pharmacokinetic data available for rabbits.