Gamithromycin   中文名称: 加米霉素

MmmSC strain B237(MIC= 0.00012 μg/mL);MmmSC strain Tan8(MIC= 0.00006μg/mL )
Bacterial 50S ribosomal subunit (inhibits bacterial protein synthesis) [1]

- 针对10株Mycoplasma mycoides subsp. mycoides Small Colony（MmmSC）菌株，加米霉素（gamithromycin） 的最低抑菌浓度（MIC）范围为0.0625–0.25 μg/mL，MIC50为0.125 μg/mL，MIC90为0.25 μg/mL（肉汤微量稀释法测定）[1]
- 时间杀菌曲线显示，加米霉素（2×MIC）对MmmSC表现为抑菌作用，孵育48小时后细菌数量减少≤1 log10 CFU/mL，无显著杀菌效果[1]
当将血清与人工培养基进行比较时，在初始接种量为 106 cfu/时，加米霉素、泰乐菌素和替米考星对 MmmSC 菌株 B237 的最低抑菌浓度 (MIC) 值分别低 64 倍、8 倍和 64 倍。毫升。对于 Tan8，也出现了类似的模式。与未经处理的血清或合成培养基相比，加米霉素在热灭活血清中的最低抑菌浓度 (MIC) 更高[1]。

- 在48匹患轻中度支气管肺炎的马驹中，单次皮下注射加米霉素（6 mg/kg）可改善临床症状。治疗后第7天，83%的马驹体温恢复正常，79%咳嗽减轻，75%呼吸频率恢复正常，显著高于安慰剂组（50%）[2]
- 气管支气管吸出物（TBA）细菌培养显示，治疗后第7天，67%的加米霉素处理马驹病原菌（如Streptococcus equi subsp. zooepidemicus）清除，而安慰剂组仅33%[2]
与对照马驹（41 匹中的 32 匹；78%）相比，用加米霉素 (GAM) 治疗的马驹无需改变治疗即可恢复的百分比显着较高 (P<0.048)（40 匹中的 38 匹；95%）或 AZM-RIF（40 中的 39；98%）。与对照马驹相比，用加米霉素 (GAM) 或 AZM-RIF 治疗的马驹临床评分显着降低，脓肿更少，且治疗一周和两周后脓肿评分显着降低。在治疗的第三周，加米霉素（GAM）治疗的马驹的白细胞计数显着高于AZM-RIF治疗的马驹[2]。

- MmmSC的MIC测定：细菌在改良Hayflick培养基中培养至1×10^6 CFU/mL，将加米霉素稀释为0.0078–1 μg/mL加入96孔板，接种细菌后于37°C、5% CO2孵育7天，以完全抑制生长的最低浓度为MIC[1]
- 时间杀菌实验：MmmSC培养物（5×10^5 CFU/mL）暴露于加米霉素（0.25–1 μg/mL，1×和2×MIC），37°C孵育，分别在0、24、48小时取样计数活菌数（CFU/mL）[1]
使用大量稀释技术来确定加米霉素、泰乐菌素和替米考星对 MmmSC 菌株 B237 和 Tan8 的最低抑制浓度 (MIC)。每个抗菌稀释液接受等体积的对数期 MmmSC 培养物，以提供 107 cfu/mL 的接种量，或 4 mL 体积中用于后续时间灭活测定的预期初始滴度。在 37°C 下，培养物孵育 24 小时。每隔0小时和24小时取出样品，并连续稀释10倍至10-5。将每个稀释液的等分试样 (10 μL) 移至固体培养基中，并从稀释液中计数菌落，在 37°C、含 5% 二氧化碳的潮湿气氛中孵育至少 4 天后，每板产生 30 至 300 个菌落在空中。阻止 cfu/mL 24 小时增加的最低抗菌浓度 (MIC) 定义为转换为 cfu/mL 的计数[1]。

Foals exhibiting pulmonary abscesses on ultrasonographic examinations are randomized into three treatment groups: (1) semimembranosus/semitendinosus muscles are treated with gamithromycin at a dose of 6.0 mg/kg body weight once a week (GAM; n = 40); (2) azithromycin at a dose of 10 mg/kg PO once daily combined with rifampin at a dose of 10 mg/kg PO once daily (AZM-RIF; n = 40); and (3) no antimicrobial treatment (controls; n = 41). To ensure that every foal in every treatment group receives the same daily manipulation, each foal receives acetylcysteine at a dose of 10 mg/kg PO per day[2].

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- Bronchopneumonia foal model: Foals (1–6 months old) with clinical signs (fever ≥38.5°C, cough, abnormal lung auscultation) and positive TBA bacterial culture were included. Gamithromycin (6 mg/kg) was administered as a single subcutaneous injection. Clinical parameters (temperature, respiratory rate, cough score) and TBA bacterial counts were evaluated at days 0, 1, 3, 7, and 14 [2]

In foals, after a single subcutaneous injection of gamithromycin (6 mg/kg), peak plasma concentration (Cmax) was 1.2 μg/mL at 2 hours post-dose. The drug showed high lung tissue penetration, with lung/plasma concentration ratio of 8:1 at 24 hours. Plasma half-life (t1/2) was approximately 36 hours [2]

[1]. In vitro pharmacodynamics of gamithromycin against Mycoplasma mycoides subspecies mycoides Small Colony. Vet J. 2013 Sep;197(3):806-11.

[2]. Efficacy of Gamithromycin for the Treatment of Foals with Mild to Moderate Bronchopneumonia. J Vet Intern Med. 2015 Jan-Feb; 29(1): 333–338.

Gamithromycin is a macrolide antibiotic with formula C40H76N2O12. It is used for the treatment of of bovine respiratory disease caused by Mannheimia haemolytica, Pasteurella multocida, Histophilus somni and Mycoplasma bovis in beef and non-lactating dairy cattle. The compound is also licensed in Europe for the treatment of footrot in sheep caused by Dichelobacter nodosus and Fusobacterium nodosus. It has a role as an antibacterial drug and a protein synthesis inhibitor. It is a macrolide antibiotic and a monosaccharide derivative.
Gamithromycin is an antibiotic used in cattle.

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Drug Indication
CattleTreatment and metaphylaxis of bovine respiratory disease (BRD) associated with Mannheimia haemolytica, Pasteurella multocida and Histophilus somni. The presence of the disease in the herd should be established before metaphylactic use. PigsTreatment of swine respiratory disease (SRD) associated with Actinobacillus pleuropneumoniae, Pasteurella multocida, Haemophilus parasuis and Bordetella bronchiseptica. SheepTreatment of infectious pododermatitis (foot rot) associated with virulent Dichelobacter nodosus and Fusobacterium necrophorum requiring systemic treatment.

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- Gamithromycin is a semi-synthetic macrolide antibiotic developed for veterinary use, primarily targeting gram-positive and some gram-negative respiratory pathogens [1][2]
- Its mechanism of action involves binding to the bacterial 50S ribosomal subunit, inhibiting peptide chain elongation and bacterial protein synthesis [1]

C40H76N2O12

777.05

776.539

C, 61.83; H, 9.86; N, 3.61; O, 24.71

145435-72-9

145435-72-9;

59364992

Solid powder

1.2±0.1 g/cm3

833.0±65.0 °C at 760 mmHg

457.6±34.3 °C

0.0±0.6 mmHg at 25°C

1.535

3.89

180.08

5

14

9

54

1180

18

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

VWAMTBXLZPEDQO-UZSBJOJWSA-N

InChI=1S/C40H76N2O12/c1-15-17-42-21-22(3)33(44)40(11,48)29(16-2)52-36(46)26(7)32(53-30-20-39(10,49-14)34(45)27(8)51-30)25(6)35(38(9,47)19-23(42)4)54-37-31(43)28(41(12)13)18-24(5)50-37/h22-35,37,43-45,47-48H,15-21H2,1-14H3/t22-,23+,24+,25-,26+,27-,28-,29+,30-,31+,32-,33+,34-,35+,37-,38+,39+,40+/m0/s1

(2R,3S,4R,5S,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-dimethyloxan-2-yl]oxy-3,5,8,10,12,14-hexamethyl-7-propyl-1-oxa-7-azacyclopentadecan-15-one

Gamithromycin; GAM, ML-1709460; Gamithromycin; 145435-72-9; gamitromicina; gamithromycinum; ML-1709,460; ML-460; ML-1,709,460; (2R,3S,4R,5S,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-dimethyloxan-2-yl]oxy-3,5,8,10,12,14-hexamethyl-7-propyl-1-oxa-7-azacyclopentadecan-15-one; ML 1709460; ML1709460;

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 : ~100 mg/mL ( ~128.69 mM )
Ethanol : ~100 mg/mL

配方 1 中的溶解度: ≥ 2.5 mg/mL (3.22 mM) (饱和度未知) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将100 μL 25.0 mg/mL澄清DMSO储备液加入到400 μL PEG300中，混匀；然后向上述溶液中加入50 μL Tween-80，混匀；加入450 μL生理盐水定容至1 mL。
*生理盐水的制备：将 0.9 g 氯化钠溶解在 100 mL ddH₂O中，得到澄清溶液。

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配方 2 中的溶解度: 2.5 mg/mL (3.22 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (这些助溶剂从左到右依次添加，逐一添加), 悬浊液; 超声助溶。
例如，若需制备1 mL的工作液，可将 100 μL 25.0 mg/mL澄清DMSO储备液加入900 μL 20% SBE-β-CD生理盐水溶液中，混匀。
*20% SBE-β-CD 生理盐水溶液的制备（4°C，1 周）：将 2 g SBE-β-CD 溶解于 10 mL 生理盐水中，得到澄清溶液。

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配方 3 中的溶解度: ≥ 2.5 mg/mL (3.22 mM) (饱和度未知) in 10% DMSO + 90% Corn Oil (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将 100 μL 25.0 mg/mL 澄清 DMSO 储备液加入到 900 μL 玉米油中并混合均匀。

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配方 4 中的溶解度: 10% DMSO+40% PEG300+5% Tween-80+45% Saline: ≥ 2.5 mg/mL (3.22 mM)

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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。