TYLORIC 20%

Indications

• Bacterial infections in livestock
• Respiratory infections
• Enteritis caused by various pathogens
• Mycoplasma infections

Dosage

Children: For paediatric dosing, refer to the BNF for Children for appropriate dosing information based on age and weight.

Adults: Refer to the BNF for specific dosing guidelines based on the condition being treated, as doses may vary.

Mechanism of action

Tylosin inhibits peptide bond formation by binding to the 50S ribosomal subunit of bacteria, blocking the aminoacyl-tRNA from entering the ribosome and thus halting protein synthesis. This inhibition acts as a slow-binding, slowly reversible process, and the interaction with the ribosome is characterized by a significant degree of irreversibility, which is crucial for its antibiotic properties.

Pharmacodynamics

Tylosin exhibits bacteriostatic activity, meaning it inhibits bacterial growth rather than directly killing bacteria. Its effectiveness is particularly notable against certain strains of bacteria that are resistant to other antibiotic classes. The irreversibility of its action on the ribosome contributes to its long-lasting effects against bacterial infections.

Pharmacokinetics

After administration, tylosin is absorbed and distributed throughout the body. It is metabolized in the liver and excreted primarily in the bile, with some renal excretion. The half-life of tylosin can vary based on the route of administration and the species being treated. It is important to monitor for potential accumulation in cases of renal impairment.

Pregnancy

There is insufficient data on the use of tylosin during pregnancy. It should only be used if the potential benefits outweigh the risks.

Breast-feeding

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

Storage

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

Formulations

• Tylosin tartrate tablets
• Tylosin injectable solution
• Tylosin oral suspension

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