Macrolide antibiotic

Absorption, Distribution and Excretion
Pigs were fed 154 or 400 mg of (14)C-tilmicosin in their diet, following a five-day course of the same dose. Radioactivity recoveries in urine ranged from 4% to 6%, and in feces from 62% to 75%. Radioactivity was detected in bile, but not quantitatively analyzed. Pigs were also fed 110 mg of (14)C-tilmicosin daily. Radioactivity recoveries in urine were 15%, and in feces 80%. Tilmicosin was administered subcutaneously. Absorption was rapid after injection… Biura crossbred lambs were administered 20 mg/kg body weight of (14)C-tilmicosin subcutaneously daily. The main radioactive components in the liver, kidneys, and urine were the parent drug, along with small amounts of T1 and T2, and small amounts of other unidentified substances. For more complete data (of 13) on the absorption, distribution, and excretion of tilmicosin, please visit the HSDB records page.

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Metabolism / Metabolites
Beulah hybrid lambs were subcutaneously injected daily with 20 mg/kg body weight of (14)C-tilmicosin. The main radioactive components in the liver, kidneys, and urine were the parent drug, along with small amounts of T1 and T2, and small amounts of other unidentified substances. Fischer-344 rats (10 males and 10 females) were administered 50 mg/kg body weight of (14)C-tilmicosin by gavage for 5 consecutive days. Fecal radioactivity was analyzed to detect the presence of sulfate metabolites found in pig feces, and similar compounds were found, but not quantified. Fifteen male and fifteen female Fischer-344 rats were orally administered (14)C-labeled tilmicosin (with both the normicosin macrolide ring and piperidine ring labeled) at a dose of 20 mg/kg body weight/day for 3 consecutive days. In the liver, the radiolabeled substances corresponded to tilmicosin and its demethylated derivative T1 (demethylated on the macamisose ring). The only radioactive substance detected in urine was unmetabolized tilmicosin, while the main peak in feces was the parent compound, with minor amounts of desmethyltilmicosin, and a high molecular weight compound T2 (composed of two macrocyclic lactone rings and one piperidine ring) known to exist as an impurity in the administered substance. In summarizing results from cattle injected with 14C-tilmicosin, it was reported that the radioactivity distribution in the liver of tested rats was similar to that in feces. In animals treated with high-purity tilmicosin samples, metabolite T2 was not detected in the liver, indicating its presence was due to direct administration as a drug component. Radioactivity in the kidneys was primarily in the form of unmetabolized tilmicosin. For more complete metabolite/metabolite data on 6 tilmicosins, please visit the HSDB records page.

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Biological Half-Life
The plasma half-life of macrolide antibiotics is typically 1-3 hours, ... /Macrolides/

Interactions
Concomitant use of carbamazepine, cyclosporine, digoxin, hexobarbital, phenytoin, or valproic acid with macrolide antibiotics may increase the serum concentrations of these drugs; monitoring the serum concentrations of concomitant drugs is recommended to avoid toxic reactions. Macrolide antibiotics: Concomitant use of xanthines (except dihydroxypropyltheophylline) with macrolide antibiotics may reduce the hepatic clearance of xanthines, leading to increased serum concentrations and/or toxic reactions; dose adjustments of xanthines may be necessary during and after macrolide antibiotic treatment. Macrolide antibiotics: Concomitant use of midazolam or triazolam with macrolide antibiotics may reduce the clearance of these drugs, thereby enhancing the pharmacological effects of midazolam or triazolam. Macrolide antibiotics: Concomitant use with macrolide antibiotics may increase anticoagulant effects; patients taking both anticoagulants and macrolide antibiotics should have their prothrombin time closely monitored. /Macrolide Antibiotics/
For more complete interaction data (out of 8) for tilmicosin, please visit the HSDB record page.

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Non-Human Toxicity Values
Oral LD50 in rats (non-fasting males and females) > 2000 mg/kg/bw
Oral LD50 in rats (fasting females) 800 mg/kg/bw
Oral LD50 in rats (fasting males) 850 mg/kg/bw
Subcutaneous LD50 in mice (females) 109 mg/kg/bw
For more complete (8 data points) data on non-human toxicity of tilmicosin, please visit the HSDB record page.

Antimicrobial Agents and Chemotherapy56(11),6033-6036(2012).

See also: Tilmicosin (with active component); Monensin; Tilmicosin phosphate (ingredient); Tilmicosin; Tilmicosin phosphate (ingredient).

C46H80N2O13.H3O4P

967.128

966.542

C, 57.13; H, 8.65; N, 2.90; O, 28.12; P, 3.20

137330-13-3

Tilmicosin;108050-54-0

5282522

Light yellow to yellow solid powder

1.219g/cm3

926.6ºC at 760 mmHg

514.2ºC

2.91E-11mmHg at 25°C

1.578

2.35

7

19

12

66

1470

19

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NESIVXZOSKKUDP-ARVJLQODSA-N

InChI=1S/C46H80N2O13.H3O4P/c1-13-36-33(24-57-46-44(56-12)43(55-11)40(53)31(8)59-46)19-25(2)14-15-34(49)28(5)20-32(16-17-48-22-26(3)18-27(4)23-48)42(29(6)35(50)21-37(51)60-36)61-45-41(54)38(47(9)10)39(52)30(7)58-45;1-5(2,3)4/h14-15,19,26-33,35-36,38-4

4A-O-de(2,6-dideoxy-3-C-methyl-α-L-ribo-hexopyranosyl)-20-deoxo-20-[(3R,5S)-3,5-dimethyl-1-piperidinyl]-tylosin, monophosphate

LY177370; LY 177370; Tilmicosin phosphate; 137330-13-3; LY177370 phosphate; Pulmotil 90; Micotil 300; LY-177370 phosphate; Micotil

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: Please store this product in a sealed and protected environment, avoid exposure to moisture.

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

DMSO : ≥ 100 mg/mL (~103.40 mM)
H2O : ≥ 100 mg/mL (~103.40 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (2.58 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 (2.58 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 (2.58 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: 100 mg/mL (103.40 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication.

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