ATCvet code:
QJ01FA95
Pharmacodynamics
Gamithromycin is a semi-synthetic macrolide (CAS No 145435-72-9) prepared by fermentation followed by organic synthesis. The substance is a member of the azalide subclass of macrolide antibiotics consisting of a 15-membered macrocyclic lactone ring. Macrolides in general have both bacteriostatic and bactericidal action mediated through disruption of bacterial protein synthesis. Macrolides inhibit bacterial protein biosynthesis by binding to the 50S ribosomal subunit and by preventing peptide chain elongation. The in-vitro data show that gamithromycin acts in a bactericidal manner. The broad spectrum antimicrobial activity of gamithromycin includes Mannheimia haemolytica, Pasteruella multocida, Histophilus somni, Actinobacillus pleuropneumoniae, Glaesserella parasuis and Bordetella bronchiseptica, Fusobacterium necrophorum and Dichelobacter nodosus. The MIC and MBC data (cattle and pig) are reported from a representative sample of isolates from field materials within different EU geographic areas.
Cattle | MIC90s | MBC90s |
µg/ml |
Mannheimia haemolytica | 0.5 | 1 |
Pasteurella multocida | 1 | 2 |
Histophilus somni | 1 | 2 |
Pigs | MIC90s | MBC90s |
µg/ml |
Actinobacillus pleuropneumoniae | 4 | 4 |
Pasteurella multocida | 1 | 2 |
Glaesserella parasuis | 0.5 | 0.5 |
Bordetella bronchiseptica | 2 | 4 |
Sheep | MIC |
µg/ml |
Fusobacterium necrophorum | MIC90 : 32 |
Dichelobacter nodosus | 0.008 – 0.016 |
Resistance to macrolides can develop by mutations in genes encoding ribosomal RNA (rRNA) or some ribosomal proteins; by enzymatic modification (methylation) of the 23S rRNA target site, generally giving rise to cross-resistance with lincosamides and group B streptogramins (MLSB resistance); by enzymatic inactivation; or by macrolide efflux. MLSB resistance may be constitutive or inducible. Resistance may be chromosomal or plasmid-encoded and may be transferable if associated with transposons, plasmids, integrative and conjugative elements.
Pharmacokinetics
Cattle: Gamithromycin administered subcutaneously into the neck of cattle at a single dose of 6 mg/kg body weight, resulted in rapid absorption with peak plasma concentrations observed after 30 to 60 min with a long plasma half-life (> 2 days). The bioavailability of the compound was > 98% with no gender differences. The volume of distribution at steady-state was 25 L/kg. Gamithromycin levels in lung reached a maximum in less than 24 hours, with lung-to-plasma ratio of > 264. In vitro plasma protein binding studies determined that the mean concentration of the free active substance was 74%. Biliary excretion of the unchanged drug substance was the major route of elimination.
Pigs: Gamithromycin administered intramuscularly in pigs at single dose of 6 mg/kg body weight, resulted in rapid absorption with peak plasma concentrations observed after 5 to 15 min, with a long plasma half-life (about 4 days). The bioavailability of gamithromycin was > 92%. The volume of distribution at steady-state was approximately 39 L/kg. The compound is absorbed rapidly into the lung. Accumulation of gamithromycin in the lung has been demonstrated by high and sustained concentrations in the lung and bronchial fluid which far exceed those in blood plasma. In vitro plasma protein binding studies determined that the mean concentration of the free active drug was 77%. Biliary excretion of the unchanged drug was the major route of elimination.
Sheep: Gamithromycin administered subcutaneously into the neck of sheep at a single dose of 6 mg/kg body weight is rapidly absorbed, and maximum plasma concentrations were observed between 15 minutes and 6 hours after dosing with high absolute bioavailability of 89%. Gamithromycin skin concentrations were much higher than the plasma concentrations resulting in skin/plasma concentration ratios of approximately 21, 58, and 138 at two, five, and ten days post-dosing, respectively, demonstrating extensive distribution and accumulation in skin tissue.