Tylosin

Structural formula
	Structure of the main component tylosin A
General
Non-proprietary name	Tylosin
other names	(4 R , 5 S , 6 S , 7 R , 9 R , 11 E , 13 E , 15 R , 16 R ) -15 - ([{6-Deoxy-2,3-di- O -methyl-β- D -allopyranosyl} oxy] methyl) -6- (3,6-dideoxy-4- O - (2,6-dideoxy-3- C- methyl-α- L - ribo -hexopyranosyl) -3- (dimethylamino) - β- D -glucopyranosyl] oxy) -16-ethyl-4-hydroxy-5,9,13-trimethyl-7- (2-oxoethyl) oxacyclohexadeca-11,13-diene-2,10-dione ( IUPAC , tylosin A ); 2 - [(4 R , 5 S , 6 S , 7 R , 9 R , 11 E , 13 E , 15 R , 16 R ) -6 - [(2 R , 3 R , 4 R , 5 S , 6 R ) -5 - [(2 S , 4 R , 5 S , 6 S ) -4,5-dihydroxy-4,6-dimethyloxan-2-yl] oxy-4- (dimethylamino) -3-hydroxy-6-methyloxane -2-yl] oxy-16-ethyl-4-hydroxy-15 - [{(2 R , 3 R , 4 R , 5 R , 6 R ) -5-hydroxy-3,4-dimethoxy-6-methyloxane 2-yl} oxymethyl] -5,9,13-trimethyl-2,10-dioxo-1-oxacyclohexadeca-11,13-dien-7-yl] acetaldehyde;
Molecular formula	C 46 H 77 NO 17
Brief description	almost white to pale yellow powder
External identifiers / databases
ECHA InfoCard	100.014.322
PubChem	5280440
Wikidata	Q411462
Drug information
ATC code	Q J01FA90
Drug class	Macrolides
Mechanism of action	Inhibition of protein synthesis at the 50-S ribosomal subunit
properties
Molar mass	916.11 g · mol -1
Physical state	firmly
Melting point	128-135 ° C
solubility	slightly soluble in water, easily soluble in dichloromethane and absolute ethanol
safety instructions
	Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed
GHS labeling of hazardous substances Tartrate; danger
H and P phrases	H: 317-334
	P: 261-280-342 + 311
Toxicological data	> 5000 mg kg −1 ( LD 50 , rat , oral )
	As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Tylosin is a bacteriostatic antibiotic from the class of 16-membered macrolides . It was first found in the soil in Thailand . It is obtained from Streptomyces fradiae and, in addition to the main component tylosin A, consists of 20% different proportions of desmycosin , macrocin and relomycin . The secondary components contribute to the effectiveness. Tylosin is a weak base with a pK _s value of 7.1. Chemically, it is a lactone ring with 16 atoms that is glycosidically linked to the monosaccharides mycinose , mycaminose and mycarose . Tylosin is lipophilic and therefore easily permeable to the membrane.

Tylosin in its pure form is a white to pale yellow powder that is rather poorly soluble in water, but very well soluble in ethanol and fat. The tartrate salt, on the other hand, is readily soluble in water. For the iv injection, tylosin is dissolved in a 50 percent propylene glycol solution. Tylosin is highly allergenic on skin contact .

For most gram-positive and gram-negative bacteria as well as for mycoplasma , tylosin has a minimum inhibitory concentration (MIC) of 0.2 to 0.5 μg / ml. Its pronounced post-antibiotic effect ensures an effect that goes beyond stopping the medication.

Tylosin is only approved for veterinary use and in research facilities. An application in the therapy of human Crohn's disease has recently been examined. In the first experiments, tylosin seems to be at least equivalent to metronidazole in the positive influence on enteral inflammation.

Composition of tylosin
Surname	Alternate name	Molecular formula	molar mass	proportion of
Tylosin A		C ₄₆ H ₇₇ NO ₁₇	916	at least 80%
Desmycosin	Tylosin B	C ₃₉ H ₆₅ NO ₁₄	772	maximum 20%
Macrocin	Tylosin C	C ₄₅ H ₇₅ NO ₁₇	902
Relomycin	Tylosin D	C ₄₆ H ₇₉ NO ₁₇	918

Mechanism of action

Tylosin inhibits such as erythromycin , the protein synthesis at the ribosome 50S subunit . While erythromycin only prevents the binding of peptidyl- tRNA , tylosin also blocks the binding of aminoacyl-tRNA. This more effectively hinders the transcription of important bacterial DNA information into their end products.

Resistances

The formation of resistance to tylosin occurs slowly. The transmission takes place via bacterial plasmids . It is known that enterobacteria , staphylococci , streptococci , Brachyspira ( Treponema ) hyodysenteriae and Mycoplasma gallisepticum may develop resistance . Due to the mechanism of action described above, coagulase- positive staphylococci can be resistant to erythromycin, but are sensitive to tylosin. The European Union put tylosin on the index because it was misused at the time as a performance enhancer in animal fattening. Since 1999 it has only been allowed to be administered to animals that have been diagnosed by a veterinarian. This is to protect the consumer from possible intake of tylosin with the development of resistant intestinal bacteria. A study commissioned by the EU comes to the conclusion that tylosin in low doses does not lead to the development of resistance in the human intestinal flora to enterobacteria. The indexing remains in place to be on the safe side. Since 2006, antibiotics have been banned as fattening accelerators in the EU.

Pharmacokinetics

Tylosin phosphate is poorly absorbed in the gastrointestinal tract. The tartrate form, which is particularly well absorbed in the small intestine, is suitable for oral substitution. Lower concentrations are measured in the serum than in the periphery (lungs, kidneys, liver, udder).

In the plasma, tylosin is bound to alpha-1 acid glycoprotein and albumin . Plasma protein binding is 35 to 45% in cattle and pigs . Depending on the species, tylosin is partly metabolized in the liver, 20 to 40% is excreted via the kidneys and 7 to 10% in the faeces in unchanged form.

Interactions

In essence, tylosin interacts in a similar way to erythromycin because of its chemical relationship. It inhibits the CYP3A4 enzyme system in the liver . Drugs such as lidocaine , warfarin , diazepam and others that are eliminated via this system are longer in higher effective levels under tylosin therapy. In particular, care must be taken to increase the effect of digitalis glycosides with the resulting toxicity.

laboratory

In the case of colorimetric determination of the AST / ALT, false positive values can result under therapy with tylosin. Certain deviations were also found in the fluorometric determination of catecholamines from urine.

Pathogen spectrum

Staphylococcus intermedius and Clostridium spp. Show particular sensitivity to tylosin . , in particular Clostridium perfringens , Mycoplasma spp. , gram positive cocci and Lawsonia intracellularis .

effectiveness

Tylosin has been shown to be effective against the following animal diseases:

Pig Dysentery , Porcine Intestinal Spirochätosis , Porcine Proliferative Enteritis Caused by Lawsonia intracellularis , Mycoplasma Arthritis and Polyserositis of Pig, Erysipeloid (Rotlauf) of Pig

Mycoplasma pneumonia , foot mange , metritis and gram-positive cocci mastitis in cattle and mycoplasma arthritis in calves

Campylobacter infections in sheep

Mycoplasmosis and Spirochaetosis of Poultry

Lumpy jaw disease of the kangaroo.

Trade names

Tylan, Tylosel, Tylo-Suscit

Individual evidence

↑ ^a ^b ^c data sheet TYLOSIN CRS (PDF) at EDQM , accessed on April 3, 2009.

↑ Jacek Lewicki: A review of pharmacokinetics, residues in food animals and analytical methods ( page no longer available , search in web archives ) Info: The link was automatically marked as defective. Please check the link according to the instructions and then remove this notice. (free full text access, in English).@1@ 2Template: Dead Link / ftp.fao.org

↑ ^a ^b data sheet tylosin tartrate from Sigma-Aldrich , accessed on November 3, 2016 ( PDF ).

literature

Hans-Hasso Frey and Wolfgang Löscher: Textbook of pharmacology and toxicology for veterinary medicine . Enke, Stuttgart 2002, ISBN 3-7773-1797-7 .

Web links

Entry on tylosin at Vetpharm
Knothe H. (1977): A review of the medical considerations of the use of tylosin and other macrolide antibiotics as additives in animal feeds. Infection ; 5 (3); 183-187; PMID 334674 .

[Ph._Eur.-1] ta sheet TYLOSIN CRS (PDF) at EDQM , accessed on April 3, 2009.