泰妙菌素是二萜类抗生素截短截短侧耳素的半合成衍生物，已被发现在支原体原发性颈部炎症的研究中有效[1]。泰妙菌素对阳性细菌（葡萄球菌、链球菌、梭菌、Mysterella）、螺旋体（猪腹泻短螺旋体、无性短螺旋体、毛短螺旋体和中间短螺旋体）和支原体菌株（鸡毒支原体、滑液支原体、火鸡支原体和支原体）具有革兰氏活性。 .爱荷华州）[1]。然而，泰妙菌素对革兰氏阴性菌（巴斯德氏菌、克雷伯氏菌、嗜血杆菌、梭菌、弯曲杆菌、拟杆菌）的活性降低[1]。为了允许肽酶和随后的蛋白质合成，tRNA 必须正确定位以实现 tRNA 的 CCA 终止，而 tiimulin 与核糖体肽基转移酶凹槽中的 rRNA 的结合会阻碍该终止 [1]。

在使用毛囊芽孢杆菌和中间芽孢杆菌的假感染测试中，用泰妙菌素（25 mg/kg，持续 5 天）治疗种鸡和鸡蛋中的家禽破坏性螺旋体病被证明非常成功 [1]。

Absorption, Distribution and Excretion
It is readily absorbed from the gut and can be found in the blood within 30 minutes after dosing.
Tiamulin is well absorbed orally by swine. Approximately 85% of a dose is absorbed and peak levels occur between 2-4 hours after a single oral dose. Tiamulin is apparently well distributed, with highest levels found in the lungs.
In pigs (2 animals per sex and group), following oral administration of 5 mg (14)C-tiamulin base/kg bw/day for 10 consecutive days, approximately 35% of the dose was eliminated in urine and 65% in feces. The total residue concentrations in liver, kidney, muscle and fat were 21,880, 600, 720 and 720 ug equivalents/kg, respectively, 10 days after dosing and 480, 220, 430, 910 ug equivalents/kg after 25 days.

---

Metabolism / Metabolites
In laying hens, broilers and turkeys (6 animals per group) orally dosed with 10 mg (3)H-tiamulin hydrogen fumarate/kg bw/day for 5 consecutive days, over 15 metabolites were detected in tissue extracts but most of the residue was accounted for by 4 metabolites. No individual metabolite represented more than 30% of the total residue in poultry tissues.
In the liver of pigs orally treated with tiamulin, the percentage of the metabolites that can be hydrolyzed to 8-alpha-hydroxymutilin (ie marker residue) to total residues was 3.5, 3.6 and 5.7% at 4, 24 and 96 hours after treatment, respectively.
In pigs (4 animals per sex and group) given ad libitum access to feed containing tiamulin at a concentration of 39 mg/kg for 10 consecutive days, the average concentrations of metabolites in liver that could be hydrolyzed to form 8-alpha-hydroxymutilin, as detected by gas chromatography with electrochemical detection, were 447 and 247 ug equivalent/kg at 2 and 12 hours after dosing, respectively. In animals does for 18 consecutive days, the average concentrations of 8-alpha-hydroxymutilin in liver were 184, 256, 214 and 175 ug equivalents/kg at 12, 16, 20 and 24 hours after dosing, respectively.
In pigs orally dosed with (3)H-tiamulin, 6-desmethyltiamulin accounted for less than 1% of the total residue in bile and urine samples and had 67% of the antimicrobiological activity of tiamulin when tested by agar plate diffusion. Four other metabolites were found to have antimicrobiological activities relative to tiamulin of between 0.7 and 3.3% and all other metabolites had relative activities of less than 0.3%.
Tiamulin is extensively metabolized to over 20 metabolites, some having antibacterial activity. Approximately 30% of these metabolites are excreted in the urine with the remainder excreted in the feces.

Toxicity Summary
IDENTIFICATION AND USE: Tiamulin, when administered in the drinking water for five consecutive days, is an effective antibiotic for the treatment of swine dysentery associated with Brachyspira (formerly Serpulina or Treponema) and for treatment of swine pneumonia due to Actinobacillus pleuropneumoniae. As a feed additive, it is used to cause increased weight gain in swine. HUMAN EXPOSURE AND TOXICITY: Topical administration of a 0.05% formulation of tiamulin did not cause skin irritation or sensitization. Another study was carried out in 6 healthy male human volunteers. Three volunteers were given 5 oral doses progressing from 0.125 to 7.2 mg/kg bw with 72 hours between each dose. The remaining volunteers were given a single oral dose in the range of 8.2 to 10.7 mg/kg bw tiamulin. There was no substance-related changes in blood pressure, serum chemistry or electrocardiograms. ANIMAL STUDIES: Overdoses of tiamulin have produced transitory salivation, vomiting and an apparent calming effect on the pig. In a subchronic study, rats were fed diets containing 0.5 or 30 mg tiamulin/kg bw/day for 26 weeks. Further groups of rats received 180 mg/kg bw/day for 10 weeks, followed by 270 mg/kg bw/day for 16 weeks; one group was necropsied at the end of treatment, the remaining rats were maintained on untreated control diets for a further 4 or 8 weeks. There were increases in serum cholesterol and in water intake in the 180 mg/kg bw group. When the dose was increased to 270 mg/kg bw/day, the effects included increased serum alkaline phosphatase, alanine phosphatase, alanine aminotransferase and aspartate aminotransferase. Abdominal distension, dense feces and increased urine specific gravity were also observed. Absolute and relative liver weights were increased in both sexes and fatty infiltration of the liver was observed on histopathological examination. In a chronic study, dogs were given daily oral doses of 0, 3, 10 or 30 mg/kg bw/day of tiamulin for 54 weeks. In the groups given 10 and 30 mg/kg bw/day, occasional emesis was observed, serum potassium concentrations were decreased and electrocardiograms showed prolongation of the QT interval. Serum lactate dehydrogenase (LDH) was significantly increased; there was no increase in the cardiac-related isoenzyme LDH1. Rats were fed diets containing tiamulin at concentrations designed to provide intakes of 0, 2, 8 or 32 mg/kg bw/day of tiamulin for 30 months. There was no significant dose-related trend in the incidence of any tumor type. In another study, mice were fed diets containing the equivalent of 0, 1, 6 or 48 mg/kg bw/day of tiamulin for up to 123 weeks. There was no significant dose-related trend in the incidence of any tumor type. Pregnant female rats were given daily oral doses of 0, 30, 100 or 300 mg/kg bw/day from days 6 to 15 of gestation. At 300 mg/kg bw/day there were minor signs of maternal toxicity. At this dose level, the mean fetal weight was reduced and there was an increased incidence of retarded skeletal development. There was no evidence of teratogenicity. Pregnant female rabbits were given daily oral doses of 0, 30, 55 or 100 mg/kg bw/day from days 6 to 18 of gestation. Doses of 55 mg/kg bw/day and above caused the deaths of some dams and maternal body weight gain was reduced. Litter size and fetal weights were reduced at 55 mg/kg bw/day and above. There was no evidence of teratogenicity at any dose level. Several reproductive studies were performed in pigs. Breeding sows were fed a diet containing 200 mg/kg feed from days 84 to 92 of gestation, another group was maintained on a diet containing 16 mg/kg bw/day from 2 days after mating for 6 weeks, and further groups were given tiamulin in the drinking water at a dose of 8.8 mg/kg bw/day for various periods during gestation and in some cases up to weaning of the offspring. There were no adverse effects on health of the sows, pregnancy, parturition, letter size, growth and survival of the piglets, estrus cycle or subsequent breeding performance. When given to breeding boars, at a diet containing 16 mg/kg bw/day for 14 days, there were no effects on health status, libido or semen quality. Tiamulin did not induce gene mutations in Salmonella typhimurium strains TA98, TA100, TA1535, TA1537 or TA1538. An in vitro assay for gene mutation at the HPRT locus of V79 Chinese hamster cells also gave negative results. In an in vivo micronucleus test in mice tiamulin had no effect on the frequency of micronucleated polychromatic erythrocytes.

---

Interactions
The characteristics of the toxic interaction between monensin & tiamulin were investigated in rats. A three-day comparative oral repeated-dose toxicity study was performed in Phase I, when the effects of monensin & tiamulin were studied separately (monensin 10, 30, & 50 mg/kg or tiamulin 40, 120, & 200 mg/kg body weight, respectively). In Phase II, the two compounds were administered simultaneously to study the toxic interaction (monensin 10 mg/kg & tiamulin 40 mg/kg b.w., respectively). Monensin proved to be toxic to rats at doses of 30 & 50 mg/kg. Tiamulin was well tolerated up to the dose of 200 mg/kg. After combined admin, signs of toxicity were seen (including lethality in females). Monensin caused a dose-dependent cardiotoxic effect & vacuolar degeneration of the skeletal muscles in the animals given 50 mg/kg. Both compounds exerted a toxic effect on the liver in high doses. After simultaneous admin of the two compounds, there was a mild effect on the liver (females only), hydropic degeneration of the myocardium & vacuolar degeneration of the skeletal muscles. The alteration seen in the skeletal muscles was more marked than that seen after the admin of 50 mg/kg monensin alone.
Studies were carried out to investigate the effects of monensin & tiamulin, & the simultaneous admin of both compounds on microsomal enzymes in rats. In Phase I of the experiments the effects of monensin & tiamulin were studied separately (monensin 10, 30, & 50 mg/kg or tiamulin 40, 120, & 200 mg/kg body weight, respectively), while in Phase II the two compounds were administered simultaneously (monesin 10 mg/kg & tiamulin 40 mg/kg b.w., respectively). When monensin was administered by itself, it exerted no significant effect on microsomal liver enzymes. In a few cases, slight inhibition of certain enzyme activities was seen. Tiamulin provoked a dose-dependent hepatic enzyme induction. The combined admin of monensin & tiamulin at low doses (10 & 40 mg/kg, respectively) resulted in marked elevation of P450-related enzyme activities. The enzyme induction was more pronounced in females than in males. The results suggest that the simultaneous admin of tiamulin may influence the biotransformation of monensin, possibly increasing the amount of reactive metabolite(s) of the ionophore antibiotic.
Tiamulin is an antibiotic frequently used in veterinary medicine. The drug has been shown to produce clinically important interactions with other compounds that are administered simultaneously. An NIH/3T3 cell line, stably expressing human cytochrome P450 (EC 1.14.14.1) cDNA (CYP3A4), was used to study the effect of tiamulin on CYP3A4 activity. The 6 beta-hydroxylation activity of testosterone, which is increased in CYP3A4-expressing cells compared to vector-transfected cells, showed reduced activity after incubation with 1 microM tiamulin and was completely reduced to background level after incubation with 2, 5 and 10 microM tiamulin. The CYP3A4-expressing cell line was used in combination with a shuttle vector containing the bacterial lacZ' gene to study the effect of tiamulin on CYP3A4-mediated mutagenicity of aflatoxin B1. 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.
In poultry, tiamulin interferes with monensin and salinomycin metabolism, and if the drugs are fed together, they become toxic.
For more Interactions (Complete) data for TIAMULIN (10 total), please visit the HSDB record page.

---

Non-Human Toxicity Values
LD50 Rat oral 2230 mg/kg
LD50 Rat sc 4380 mg/kg
LD50 Rat iv 20 mg/kg
LD50 Mouse oral 710 mg/kg
For more Non-Human Toxicity Values (Complete) data for TIAMULIN (15 total), please visit the HSDB record page.

[1]. Islam KM, et al. The activity and compatibility of the antibiotic tiamulin with other drugs in poultry medicine--A review. Poult Sci. 2009 Nov;88(11):2353-9.

Tiamulin is a carbotricyclic compound that is pleuromutilin in which the hydroxyacetate group is replaced by a 2-{[2-(diethylamino)ethyl]sulfanyl}acetate group. An antibacterial drug, tiamulin is used in veterinary medicine (generally as its hydrogen fumarate salt) for the treatment of swine dysentery caused by Serpulina hyodysenteriae. It has a role as an antibacterial drug. It is a carbotricyclic compound, a carboxylic ester, a cyclic ketone, a tertiary amino compound, a secondary alcohol, an organic sulfide, a tetracyclic diterpenoid and a semisynthetic derivative. It is functionally related to a Pleuromutilin.
Tiamulin is a pleuromutilin antibiotic drug that is used in veterinary medicine particularly for pigs and poultry.
See also: Tiamulin Fumarate (has salt form); Chlortetracycline; Tiamulin (component of).

---

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.

---

Therapeutic Uses
Anti-Bacterial Agents
MEDICATION (VET): Denagard (tiamulin), when administered in the drinking water for five consecutive days, is an effective antibiotic for the treatment of swine dysentery associated with Brachyspira (formerly Serpulina or Treponema) hyodysenteriae susceptible to tiamulin at a dose level of 3.5 mg tiamulin hydrogen fumarate per pound of body weight daily and for treatment of swine pneumonia due to Actinobacillus pleuropneumoniae susceptible to tiamulin when given at 10.5 mg tiamulin hydrogen fumarate per pound of body weight daily. /Included in US product label/
MEDICATION (VET): Tiamulin is a diterpenic veterinary drug widely used in swine for the control of infectious diseases, including swine dysentery & enzootic pneumonia.
MEDICATION (VET): In veterinary medicine, tiamulin is used for treatment and prophylaxis of dysentery, pneumonia and mycoplasmal infections in pigs and poultry.

---

Drug Warnings
For use in animals only - Not for human use.
Swine being treated with Denagard (tiamulin) should not have access to feeds containing polyether ionophores (e.g., monensin, lasalocid, narasin, salinomycin and semduramicin) as adverse reactions may occur.
Adverse effects occurring with this drug at usual doses are considered unlikely. Rarely, redness of the skin, primarily over the ham and underline, has been observed. It is recommended to discontinue the medication, provide clean drinking water, and hose down the area or move affected animals to clean pens.
In poultry, tiamulin interferes with monensin and salinomycin metabolism, and if the drugs are fed together, they become toxic.
Swine being treated with Denagard (tiamulin) should not have access to feeds containing polyether ionophores (e.g., monensin, lasalocid, narasin, salinomycin and semduramicin) as adverse reactions may occur.

C28H47NO4S

493.7421

493.322

C, 68.11; H, 9.60; N, 2.84; O, 12.96; S, 6.49

55297-95-5

Tiamulin fumarate;55297-96-6

656958

Sticky, translucent yellowish mass

1.1±0.1 g/cm3

563.0±50.0 °C at 760 mmHg

147-148ºC

294.3±30.1 °C

0.0±3.5 mmHg at 25°C

1.541

5.93

92.14

1

6

10

34

770

8

S(C([H])([H])C([H])([H])N(C([H])([H])C([H])([H])[H])C([H])([H])C([H])([H])[H])C([H])([H])C(=O)O[C@]1([H])C([H])([H])[C@](C([H])=C([H])[H])(C([H])([H])[H])[C@]([H])([C@]([H])(C([H])([H])[H])[C@]23C([H])([H])C([H])([H])C([C@@]2([H])C1(C([H])([H])[H])C([H])(C([H])([H])[H])C([H])([H])C3([H])[H])=O)O[H]

UURAUHCOJAIIRQ-KWVPEQCVSA-N

InChI=1S/C28H47NO4S/c1-8-26(6)17-22(33-23(31)18-34-16-15-29(9-2)10-3)27(7)19(4)11-13-28(20(5)25(26)32)14-12-21(30)24(27)28/h8,19-20,22,24-25,32H,1,9-18H2,2-7H3/t19-,20+,22-,24+,25+,26-,27-,28+/m1/s1

(3aS,4R,5S,6S,8R,9S,9aR,10R)-2-[[2-(Diethylamino)ethyl]thio]acetic Acid 6-Ethenyldecahydro-5-hydroxy-4,6,9,10-tetramethyl-1-oxo-3a,9-propano-3aH-cyclopentacycloocten-8-yl Ester

SQ 14055; SQ-14055; SQ14055; Tiamulin;

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 : ~98 mg/mL ( ~198.48 mM )
Water : ~98 mg/mL
Ethanol : ~98 mg/mL

注意: 如下所列的是一些常用的体内动物实验溶解配方，主要用于溶解难溶或不溶于水的产品（水溶度<1 mg/mL）。 建议您先取少量样品进行尝试，如该配方可行，再根据实验需求增加样品量。

---

注射用配方1: DMSO : Tween 80： Saline = 10 : 5 : 85 (如： 100 μL DMSO → 50 μL Tween 80 → 850 μL Saline)
*生理盐水/Saline的制备：将0.9g氯化钠/NaCl溶解在100 mL ddH ₂ O中，得到澄清溶液。
注射用配方 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (如： 100 μL DMSO → 400 μL PEG300 → 50 μL Tween 80 → 450 μL Saline)
注射用配方 3: DMSO : Corn oil = 10 : 90 (如： 100 μL DMSO → 900 μL Corn oil)
示例: 以注射用配方 3 (DMSO : Corn oil = 10 : 90) 为例说明, 如果要配制 1 mL 2.5 mg/mL的工作液, 您可以取 100 μL 25 mg/mL 澄清的 DMSO 储备液，加到 900 μL Corn oil/玉米油中, 混合均匀。

View More

注射用配方 4: DMSO : 20% SBE-β-CD in Saline = 10 : 90 [如：100 μL DMSO → 900 μL (20% SBE-β-CD in Saline)]
*20% SBE-β-CD in Saline的制备（4°C，储存1周）：将2g SBE-β-CD (磺丁基-β-环糊精) 溶解于10mL生理盐水中，得到澄清溶液。
注射用配方 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (如： 500 μL 2-Hydroxypropyl-β-cyclodextrin (羟丙基环胡精)→ 500 μL Saline)
注射用配方 6: DMSO : PEG300 : Castor oil : Saline = 5 : 10 : 20 : 65 (如： 50 μL DMSO → 100 μL PEG300 → 200 μL Castor oil → 650 μL Saline)
注射用配方 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (如： 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
注射用配方 8: 溶解于Cremophor/Ethanol (50 : 50), 然后用生理盐水稀释。
注射用配方 9: EtOH : Corn oil = 10 : 90 (如： 100 μL EtOH → 900 μL Corn oil)
注射用配方 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (如： 100 μL EtOH → 400 μL PEG300 → 50 μL Tween 80 → 450 μL Saline)

---

口服配方 1: 悬浮于0.5% CMC Na (羧甲基纤维素钠)
口服配方 2: 悬浮于0.5% Carboxymethyl cellulose (羧甲基纤维素)
示例: 以口服配方 1 (悬浮于 0.5% CMC Na)为例说明, 如果要配制 100 mL 2.5 mg/mL 的工作液, 您可以先取0.5g CMC Na并将其溶解于100mL ddH2O中，得到0.5%CMC-Na澄清溶液；然后将250 mg待测化合物加到100 mL前述 0.5%CMC Na溶液中，得到悬浮液。

View More

口服配方 3: 溶解于 PEG400 (聚乙二醇400)
口服配方 4: 悬浮于0.2% Carboxymethyl cellulose (羧甲基纤维素)
口服配方 5: 溶解于0.25% Tween 80 and 0.5% Carboxymethyl cellulose (羧甲基纤维素)
口服配方 6: 做成粉末与食物混合

---

注意: 以上为较为常见方法，仅供参考， InvivoChem并未独立验证这些配方的准确性。具体溶剂的选择首先应参照文献已报道溶解方法、配方或剂型，对于某些尚未有文献报道溶解方法的化合物，需通过前期实验来确定（建议先取少量样品进行尝试），包括产品的溶解情况、梯度设置、动物的耐受性等。

---

请根据您的实验动物和给药方式选择适当的溶解配方/方案：
1、请先配制澄清的储备液(如：用DMSO配置50 或 100 mg/mL母液(储备液));
2、取适量母液，按从左到右的顺序依次添加助溶剂，澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明，并不一定代表此产品 的实际溶解配方):
10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline);
假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀/澄清；向上述体系中加入50 μL Tween-80，混合均匀/澄清；然后继续加入450 μL ddH2O (或 saline)定容至 1 mL；
3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例;
4、 如产品在配制过程中出现沉淀/析出，可通过加热(≤50℃)或超声的方式助溶;
5、为保证最佳实验结果，工作液请现配现用！
6、如不确定怎么将母液配置成体内动物实验的工作液，请查看说明书或联系我们;
7、 以上所有助溶剂都可在 Invivochem.cn网站购买。