Batimulin Powder 45%

Indications

• Bacterial infections in livestock
• Respiratory diseases in pigs
• Enteritis in poultry

Dosage

Children: Refer to the BNF for Children for appropriate dosing guidelines in pediatric patients.

Adults: Refer to the BNF for specific dosing regimens based on the indication and patient characteristics.

Mechanism of action

Tiamulin functions by inhibiting the activity of cytochrome P-450 enzymes, particularly CYP3A4, thereby affecting drug metabolism. This inhibition occurs through the formation of a metabolic intermediate complex that stabilizes CYP3A4 protein, ultimately reducing the mutation frequency associated with aflatoxin B1 in CYP3A4-expressing cells.

Pharmacodynamics

Tiamulin exhibits antibacterial activity by targeting the bacterial protein synthesis process, specifically binding to the 50S ribosomal subunit. This action disrupts the translation process, thereby inhibiting the growth of susceptible bacteria. Its effectiveness against anaerobic bacteria and certain gram-positive organisms makes it a valuable treatment option in veterinary medicine.

Pharmacokinetics

Tiamulin is absorbed following oral administration, with its pharmacokinetic profile characterized by variable bioavailability. It is extensively metabolized in the liver, primarily via cytochrome P-450 pathways. The drug has a relatively short half-life, necessitating multiple doses for effective therapeutic outcomes. It is excreted mainly through urine and feces, and its distribution in tissues is influenced by its lipophilic nature.

Pregnancy

Tiamulin should only be used during pregnancy if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

Tiamulin is not recommended during breastfeeding due to the potential for serious adverse reactions in nursing infants.

Storage

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

Mechanism of action

The mutation frequency of aflatoxin B1 could be completely inhibited by tiamulin in CYP3A4-expressing cells, but no effect was observed on the mutation frequency of the direct mutagen ethylmethanesulphonate. Western blotting of homogenates of the CYP3A4-expressing cell line showed stabilization of CYP3A4 protein after incubation with tiamulin, supporting the hypothesis that the mechanism of inhibition is by binding of tiamulin to the cytochrome. Tiamulin is a semisynthetic diterpene antibiotic frequently used in farm animals. The drug has been shown to produce clinically important--often lethal--interactions with other compounds. It has been suggested that this is caused by a selective inhibition of oxidative drug metabolism via the formation of a cytochrome P-450 metabolic intermediate complex. In the present study, rats were treated orally for 6 days with tiamulin at two different doses: 40 & 226 mg/kg of body weight. For comparison, another group received 300 mg of triacetyloleandomycin (TAO) per kg, which is equivalent to the 226-mg/kg tiamulin group. Subsequently, microsomal P-450 contents, P-450 enzyme activities, metabolic intermediate complex spectra, & P-450 apoprotein concentrations were assessed. In addition, effects on individual microsomal P-450 activities were studied in control microsomes at different tiamulin & substrate concentrations. In the rats treated with tiamulin, a dose-dependent complex formation as evidenced by its absorption spectrum & an increase in cytochrome P-4503A1/2 contents as assessed by Western blotting (immunoblotting) were found. The effects were comparable to those of TAO. Tiamulin induced microsomal P-450 content, testosterone 6 beta-hydroxylation rate, erythromycin N-demethylation rate, & the ethoxyresorufin O-deethylation activity. Other activities were not affected or decreased. When tiamulin was added to microsomes of control rats, the testosterone 6 beta-hydroxylation rate & the erythromycin N-demethylation were strongly inhibited. It is concluded that tiamulin is a potent & selective inducer-inhibitor of cytochrome P-450. Though not belonging to the macrolides, the compound produces an effect on P-450 similar to those of TAO & related compounds.