Tylokel 20

Indications

• Bacterial infections in livestock
• Treatment of respiratory diseases caused by Mycoplasma
• Control of enteric diseases in poultry
• Prevention of mastitis in dairy cattle

Dosage

Children: Refer to the BNF for Children for appropriate paediatric dosing guidelines.

Adults: Refer to specific guidelines for adult dosing as per BNF recommendations.

Mechanism of action

Tylosin inhibits peptide bond formation by binding to the ribosomal RNA of the 50S subunit of the bacterial ribosome. This inhibition is characterized as a slow-binding, slowly reversible process, where tylosin interacts with the AcPhe-tRNA. poly(U).70S ribosome complex, leading to the formation of a tight inactive complex that prevents peptide bond formation. This mechanism highlights the antibiotic's ability to interfere with bacterial protein synthesis, which is critical for bacterial growth and reproduction.

Pharmacodynamics

Tylosin exhibits bacteriostatic properties, meaning it inhibits the growth and reproduction of bacteria rather than killing them outright. Its activity is primarily against Gram-positive bacteria, including strains of Streptococcus and Staphylococcus, as well as some Mycoplasma species. The irreversibility of the tylosin effect on peptide bond formation contributes to its long-lasting antibacterial effects.

Pharmacokinetics

Tylosin is well-absorbed after administration and is widely distributed in tissues. It is metabolized in the liver, and the metabolites are excreted primarily through the urine and feces. The half-life of tylosin varies depending on the route of administration and the species being treated, but it generally shows a prolonged effect due to its binding to ribosomal sites.

Pregnancy

The safety of tylosin during pregnancy has not been established. Use only if potential benefits justify the risks.

Breast-feeding

It is not known whether tylosin is excreted in human milk. Caution is advised when administering to nursing mothers.

Storage

Store in a cool, dry place, protected from light. Keep out of reach of children.

Formulations

• Injectable solution
• Oral powder

Mechanism of action

The inhibition of peptide bond formation by tylosin, a 16-membered ring macrolide, was studied in a model system derived from Escherichia coli. In this cell-free system, a peptide bond is formed between puromycin (acceptor substrate) and AcPhe-tRNA (donor substrate) bound at the P-site of poly(U)-programmed ribosomes. It is shown that tylosin inhibits puromycin reaction as a slow-binding, slowly reversible inhibitor. Detailed kinetic analysis reveals that tylosin (I) reacts rapidly with complex C, i.e., the AcPhe-tRNA. poly(U).70S ribosome complex, to form the encounter complex CI, which then undergoes a slow isomerization and is converted to a tight complex, CI, inactive toward puromycin. These events are described by the scheme C + I <==> (K(i)) CI <==> (k(4), k(5)) CI. The K(i), k(4), and k(5) values are equal to 3 microM, 1.5 min(-1), and 2.5 x 10(-3) min(-1), respectively. The extremely low value of k(5) implies that the inactivation of complex C by tylosin is almost irreversible. The irreversibility of the tylosin effect on peptide bond formation is significant for the interpretation of this antibiotic's therapeutic properties; it also renders the tylosin reaction a useful tool in the study of other macrolides failing to inhibit the puromycin reaction but competing with tylosin for common binding sites on the ribosome. Thus, the tylosin reaction, in conjunction with the puromycin reaction, was applied to investigate the erythromycin mode of action. It is shown that erythromycin (Er), like tylosin, interacts with complex C according to the kinetic scheme C + Er <==> (K(er)) CEr <==> (k(6), k(7)) C*Er and forms a tight complex, CEr, which remains active toward puromycin. The determination of K(er), k(6), and k(7) enables us to classify erythromycin as a slow-binding ligand of ribosomes