Macrolide

Tulathromycin A, also referred to as tulathromycin, is the first member of a recently discovered macrolide subclass called triamilides[1].
Tulathromycin A (0.02 to 2.0 mg/mL) causes neutrophils to undergo concentration- and time-dependent apoptosis, which facilitates macrophage clearance of the cells afterward[3].

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Tulathromycin inhibits bacterial protein synthesis in an in vitro transcription/translation assay using Escherichia coli ribosomes and a green fluorescent protein (GFP) reporter, with an IC50 of 0.26 ± 0.05 μM. [2]
The drug shows antibacterial activity against susceptible bacterial strains. For Mannheimia haemolytica 11935, the MIC is 0.5 μg/ml; for Pasteurella multocida 4407, the MIC is 2 μg/ml; for wild-type E. coli ATCC 25922, the MIC is 16 μg/ml. [2]
Mutations or methylations at key 23S rRNA nucleotides (e.g., G745, G748, A752, A2058) in recombinant E. coli strains lead to increased MICs, indicating reduced binding and resistance. For example, in the hyperpermeable E. coli AS19rlmA strain, the MIC for tulathromycin increases from 1 μg/ml (wild-type rRNA) to 1,024 μg/ml when nucleotide A2058 is monomethylated. [2]
Unlike tilmicosin and tildipirosin, the binding of tulathromycin to the ribosome is not synergistically affected by the combination of methylations at both G748 and A2058, likely because its structure is too small to contact both nucleotides simultaneously. [2]

Tulathromycin A (2.5 mg/kg, IM) in the lungs of pigs challenged with A pleuropneumoniae and zymosan inhibits the production of proinflammatory leukotriene B4 and promotes leukocyte apoptosis and efferocytosis, while simultaneously reducing leukocyte necrosis in comparison to control pigs. In pigs inoculated with A pleuropneumoniae, tulathromycin A also reduces the extent of lung damage and lesion progression[3].

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In healthy mice, a single subcutaneous administration of Tulathromycin at 7 mg/kg resulted in rapid distribution to lung tissue, with high concentrations persisting for up to 144 hours. The drug was also rapidly absorbed into plasma, reaching peak concentrations within 30 minutes to 1 hour. [1]
In mice challenged intranasally with Escherichia coli LPS, Tulathromycin showed similar distribution and persistence in lung tissue, regardless of whether the animals were neutrophilic or neutropenic. Neutrophils did not appear to influence lung accumulation of the drug. [1]

Female BALB/c mice were randomly assigned to four treatment groups: T-7 (7 mg/kg tulathromycin), T-28 (28 mg/kg tulathromycin), T-7-LPS (7 mg/kg tulathromycin + intranasal LPS challenge), and T-7-LPS-CP (7 mg/kg tulathromycin + LPS + cyclophosphamide-induced neutropenia). LPS was administered intranasally 7 hours before tulathromycin injection. Cyclophosphamide was given intraperitoneally at 150 mg/kg on days -4, -1, and -2 relative to tulathromycin administration. Tulathromycin was administered subcutaneously in the interscapular region. Blood and lung tissues were collected at multiple time points up to 144 hours post-dose for pharmacokinetic analysis. [1]

In mice, turamycin is rapidly absorbed after subcutaneous injection, with peak plasma concentrations reached within 30 minutes to 1 hour. [1]
The drug is widely and rapidly distributed in lung tissue, with lung tissue concentrations significantly higher than plasma concentrations at all time points. [1]
The mean residence time (MRT) of turamycin in lung tissue ranged from 138 to 287 hours, indicating its long persistence. [1]
The lung/plasma AUC_0-144 ratio was 7.95 in the 7 mg/kg dose group and 5.77 in the 28 mg/kg dose group. [1]
In LPS-stimulated mice, plasma AUC_0-144 values were higher than in healthy mice, but lung tissue AUC_0-144 values were lower, suggesting that drug distribution is altered under inflammatory conditions. [1]

[1]. Pharmacokinetics of tulathromycin in healthy and neutropenic mice challenged intranasally with lipopolysaccharide from Escherichia coli. Antimicrob Agents Chemother. 2012;56(8):4078-4086.

[2]. Inhibition of protein synthesis on the ribosome by tildipirosin compared with other veterinary macrolides. Antimicrob Agents Chemother. 2012;56(11):6033-6036.

[3]. Immunomodulatory effects of tulathromycin on apoptosis, efferocytosis, and proinflammatory leukotriene B4 production in leukocytes from Actinobacillus pleuropneumoniae-or zymosan-challenged pigs. Am J Vet Res. 2015;76(6):507-519.

[4]. Vet Ther. 2005 Summer;6(2):96-112

Tulathromycin A is an aminoglycoside antibiotic. See also: Ketoprofen; Tulathromycin (ingredients); Tulathromycin A (note moved to). Indications: Cattle: For the treatment and prevention of bovine respiratory disease (BRD) caused by Tulathromycin-sensitive hemolytic Mansonia, Pasteurella multocida, Haemophilus influenzae, and Mycoplasma bovis. The presence of the disease in the herd should be determined before prophylactic treatment. For the treatment of infectious bovine keratoconjunctivitis (IBK) caused by Tulathromycin-sensitive Moraxella bovis. Pigs: For the treatment and prevention of swine respiratory disease (SRD) caused by Actinobacillus pleuropneumoniae, Pasteurella multocida, Mycoplasma hyopneumoniae, Haemophilus parasuis, and Tulathromycin-sensitive Bordetella bronchiseptica. The presence of the disease in the herd should be determined before prophylactic treatment. This product is only indicated if pigs are expected to develop the disease within 2-3 days. Sheep: Used to treat early-stage infectious plantar dermatitis (hoof rot) caused by highly virulent Clostridium nodosus, a disease requiring systemic treatment. Cattle: Used to treat and prevent bovine respiratory disease (BRD) caused by Mannheimia haemolytica, Pasteurella multocida, Histophilus somni, and Mycoplasma bovis susceptible to Tulathromycin. The presence of the disease in the herd should be determined before administering preventative treatment. Used to treat infectious bovine keratoconjunctivitis (IBK) caused by Moraxella bovis susceptible to Tulathromycin. Pigs: Used for the treatment and prevention of swine respiratory disease (SRD) caused by Actinobacillus pleuropneumoniae, Pasteurella multocida, Mycoplasma hyopneumoniae, Haemophilus parasuis, and Bordetella. Also for bronchial septicemia sensitive to Tulathromycin. Before administering prophylactic treatment, the presence of the disease in the herd should be determined. This product is only applicable when pigs are expected to develop the disease within 2-3 days. Sheep: Used to treat the early stages of infectious plantar dermatitis (hoof rot) caused by highly virulent Clostridium nodosa, which requires systemic treatment. Cattle: Used for the treatment and prevention of bovine respiratory disease (BRD) caused by hemolytic Mannsella, Pasteurella multocida, Haemophilus, and Mycoplasma bovis sensitive to Tulathromycin. Before administering prophylactic treatment, the presence of the disease in the herd should be determined. For the treatment of infectious bovine keratoconjunctivitis (IBK) caused by Morella bovis susceptible to Tulathromycin. For pigs: Treatment and prevention of porcine respiratory disease (SRD) caused by Actinomyces pleuropneumoniae, Pasteurella multocida, Mycoplasma hyopneumoniae, Haemophilus parasuis, and Bordezoella bronchiseptica susceptible to Tulathromycin. Before administering preventative treatment, the presence of the disease in the herd should be determined. This product is only applicable when pigs are expected to develop symptoms within 2-3 days. For sheep: Treatment of early infectious plantar dermatitis (hoof rot) caused by highly virulent Clostridium nodosus, which requires systemic treatment. For cattle: Treatment and prevention of bovine respiratory disease (BRD) caused by Mannheimia haemolytica, Pasteurella multocida, Histophilus somni, and Mycoplasma bovis susceptible to Tulathromycin. Before administering preventative treatment, the presence of the disease in the herd should be determined. Used to treat infectious bovine keratoconjunctivitis (IBK) caused by Moraxella bovis, which is susceptible to Tulathromycin. Pigs: Used to treat and prevent swine respiratory disease (SRD) caused by Actinobacillus pleuropneumoniae, Pasteurella multocida, Mycoplasma hyopneumoniae, Haemophilus parasuis, and Bordetella. Also used for bronchial septicemia susceptible to Tulathromycin. Before administering preventative treatment, the presence of the disease in the herd should be determined. This product is only applicable when pigs are expected to develop the disease within 2-3 days. Sheep: Used to treat the early stages of infectious plantar dermatitis (hoof rot) caused by highly virulent Clostridium nodosa, a disease requiring systemic treatment. Cattle: For the treatment and prevention of bovine respiratory disease (BRD) caused by hemolytic Mansonia solani, Pasteurella multocida, Haemophilus influenzae, and Mycoplasma bovis susceptible to Tulathromycin. The presence of the disease in the herd should be determined before prophylactic treatment. Also for the treatment of infectious bovine keratoconjunctivitis (IBK) caused by Moraxella bovis susceptible to Tulathromycin. Pigs: For the treatment and prevention of swine respiratory disease (SRD) caused by Actinobacillus pleuropneumoniae, Pasteurella multocida, Mycoplasma hyopneumoniae, Haemophilus parasuis, and Bordetella bronchiseptica susceptible to Tulathromycin. The presence of the disease in the herd should be determined before prophylactic treatment. This product is only applicable when pigs are expected to develop symptoms within 2-3 days. Sheep: For the treatment of early infectious plantar dermatitis (hoof rot) caused by highly virulent Clostridium dichotomum, which requires systemic treatment. Cattle: Used for the treatment and prevention of bovine respiratory disease (BRD) caused by Mannheimia haemolytica, Pasteurella multocida, Histophilus somni, and Mycoplasma bovis susceptible to Tulathromycin. The presence of the disease in the herd should be determined before prophylactic treatment. Also used to treat infectious bovine keratoconjunctivitis (IBK) caused by Moraxella bovis susceptible to Tulathromycin. Pigs: Used for the treatment and prevention of swine respiratory disease (SRD) caused by Actinobacillus pleuropneumoniae, Pasteurella multocida, Mycoplasma hyopneumoniae, Haemophilus parasuis, and Bordetella. For bronchial septicemia sensitive to Tulathromycin. Before administering prophylactic treatment, the presence of the disease in the herd should be determined. Draxxin should only be used if pigs are expected to develop symptoms within 2-3 days. Sheep: For the treatment of early stages of infectious plantar dermatitis (hoof rot) associated with highly virulent Clostridium nodosa, requiring systemic treatment. Cattle: For the treatment and prevention of bovine respiratory disease (BRD) associated with hemolytic Mansonia, Pasteurella multocida, Haemophilus influenzae, and Mycoplasma bovis sensitive to Tulathromycin. Before administering prophylactic treatment, the presence of the disease in the herd should be determined. For the treatment of infectious bovine keratoconjunctivitis (IBK) associated with Moraxella bovis sensitive to Tulathromycin. Pigs: For the treatment and prevention of swine respiratory disease (SRD) caused by Actinobacillus pleuropneumoniae, Pasteurella multocida, Mycoplasma hyopneumoniae, Haemophilus parasuis, and Bordetella bronchiseptica sensitive to Tulathromycin. Before administering preventative treatment, it should be determined whether the disease is present in the herd. This product is only applicable to cases where pigs are expected to develop the disease within 2-3 days. Sheep: Used to treat early infectious plantar dermatitis (hoof rot) caused by highly virulent Clostridium dichotomum, which requires systemic treatment. Tulathromycin is a semi-synthetic 15-membered ring macrolide antibiotic belonging to the triamide class. It is approved for the treatment of respiratory diseases in cattle and pigs. [1] The drug is characterized by high absorption, large volume of distribution, and long duration of action in lung tissue. [1] The mechanism of lung accumulation is not fully understood, but it may be related to uptake by inflammatory cells such as alveolar macrophages and neutrophils. [1] In this study, neutrophils had no significant effect on the accumulation of Tulathromycin in mouse lung tissue, suggesting that adjusting the dosage based on neutrophil count may not be appropriate. [1]

C41H79N3O12

806.0789

805.566

C, 61.09; H, 9.88; N, 5.21; O, 23.82

217500-96-4

9832301

Solid powder

1.2±0.1 g/cm3

853.8±65.0 °C at 760 mmHg

470.2±34.3 °C

0.0±0.6 mmHg at 25°C

1.536

4.07

7

15

11

56

1240

18

O([C@@]1([H])C([H])([H])[C@](C([H])([H])[H])([C@](C([H])([H])N([H])C([H])([H])C([H])([H])C([H])([H])[H])([C@]([H])(C([H])([H])[H])O1)O[H])OC([H])([H])[H])[C@]1([H])[C@]([H])(C(=O)O[C@]([H])(C([H])([H])C([H])([H])[H])[C@](C([H])([H])[H])([C@@]([H])([C@@]([H])(C([H])([H])[H])N([H])C([H])([H])[C@]([H])(C([H])([H])[H])C([H])([H])[C@](C([H])([H])[H])([C@@]([H])([C@@]1([H])C([H])([H])[H])O[C@@]1([H])[C@@]([H])([C@]([H])(C([H])([H])[C@@]([H])(C([H])([H])[H])O1)N(C([H])([H])[H])C([H])([H])[H])O[H])O[H])O[H])O[H])C([H])([H])[H]

GUARTUJKFNAVIK-QPTWMBCESA-N

InChI=1S/C41H79N3O12/c1-15-17-42-22-41(50)28(8)53-31(20-39(41,10)51-14)55-33-25(5)35(56-37-32(45)29(44(12)13)18-24(4)52-37)38(9,48)19-23(3)21-43-27(7)34(46)40(11,49)30(16-2)54-36(47)26(33)6/h23-35,37,42-43,45-46,48-50H,15-22H2,1-14H3/t23-,24-,25+,26-,27-,28+,29+,30-,31+,32-,33+,34-,35-,37+,38-,39-,40-,41+/m1/s1

(2R,3S,4R,5R,8R,10R,11R,12S,13S,14R)-11-[(2S,3R,4S,6R)-4-(Dimethylamino)-3-hydroxy-6-methyloxan-2-yl]oxy-2-ethyl-3,4,10-trihydroxy-13-[(2R,4R,5S,6S)-5-hydroxy-4-methoxy-4,6-dimethyl-5-(propylaminomethyl)oxan-2-yl]oxy-3,5,8,10,12,14-hexamethyl-1-oxa-6-azacyclopentadecan-15-one

CP-472,295; CP-472295; CP 472295; CP472295; Tulathromycin; Draxxin; Tulathromycin A;

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : 50~100 mg/mL ( 62.03~124.05 mM )
Ethanol : ~100 mg/mL

Solubility in Formulation 1: ≥ 2.5 mg/mL (3.10 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (3.10 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.5 mg/mL (3.10 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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Solubility in Formulation 4: 10% DMSO+40% PEG300+5% Tween-80+45% Saline: ≥ 2.5 mg/mL (3.10 mM)

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 (Please use freshly prepared in vivo formulations for optimal results.)