(4R,5S,6S,7R,9R,11Z,13Z,15R,16R)-6-[(2R,3R,4S,5S,6R)-4-(dimethylamino)-3,5-dihydroxy-6-methyloxan-2-yl]oxy-7-[2-[(3R,5S)-3,5-dimethylpiperidin-1-yl]ethyl]-16-ethyl-4-hydroxy-15-[[(2R,3R,4R,5R,6R)-5-hydroxy-3,4-dimethoxy-6-methyloxan-2-yl]oxymethyl]-5,9,13-trimethyl-1-oxacyclohexadeca-11,13-diene-2,10-dione | 108050-54-0

• 物质功能分类: 原料药 - 抗生素类药物 - 头孢菌素类药
• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (4R,5S,6S,7R,9R,11Z,13Z,15R,16R)-6-[(2R,3R,4S,5S,6R)-4-(dimethylamino)-3,5-dihydroxy-6-methyloxan-2-yl]oxy-7-[2-[(3R,5S)-3,5-dimethylpiperidin-1-yl]ethyl]-16-ethyl-4-hydroxy-15-[[(2R,3R,4R,5R,6R)-5-hydroxy-3,4-dimethoxy-6-methyloxan-2-yl]oxymethyl]-5,9,13-trimethyl-1-oxacyclohexadeca-11,13-diene-2,10-dione
• CAS: 108050-54-0
• 化学式: C₄₆H₈₀N₂O₁₃
• 分子量: 869.1
• InChiKey: JTSDBFGMPLKDCD-BRKHVWOYSA-N

物化性质

• 熔点：
  >97°C (dec.)
• 比旋光度：
  D23 +12.75° (c = 0.010004 in CHCl3, 5 cm)
• 沸点：
  926.6±65.0 °C(Predicted)
• 密度：
  1.18±0.1 g/cm3(Predicted)
• 溶解度：
  丙酮（微溶）、DMSO（微溶）、甲醇（微溶）
• 蒸汽压力：
  4.6X10-32 mm Hg at 25 °C (est)
• 旋光度：
  Specific optical rotation = +12.75 °For D (sodium) line at 23 °C (c = 0.010004 in CHCl3, 5 cm)
• 解离常数：
  pKa = 8.18 (tertiary amine)

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  61
• 可旋转键数：
  12
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.87
• 拓扑面积：
  186
• 氢给体数：
  4
• 氢受体数：
  15

ADMET

代谢

比尤拉十字羔羊接受了单次皮下注射，剂量为每千克体重20毫克/天（14）C-蒂尔米科辛。肝脏、肾脏和尿液中主要的放射性成分是母药，以及少量的T1和T2，还有少量其他未识别的物质。

Beulah cross lambs were administered a single subcutaneous dose of 20 mg/kg bw per day (14)C-tilmicosin. The major radioactive component in the liver, kidneys and urine was the parent drug, together with lesser amounts of T1 and T2, and minor amounts of other unidentified substances.

来源:Hazardous Substances Data Bank (HSDB)

代谢

费希尔-344大鼠（10只雄性和10只雌性）每天经口灌胃给予50毫克/千克体重的（14）C-蒂利霉素，持续5天。对粪便中硫酸盐代谢物的粪便放射性进行分析，发现猪粪便中存在类似的化合物，但未进行量化。

Fischer-344 rats (10 males and 10 females) were given gavage doses of 50 mg/kg bw per day (14)C-tilmicosin for 5 days. An analysis of fecal radioactivity for the presence of the sulfate metabolite that was found in the feces of pigs revealed the presence of a similar compound, but quantification was not undertaken.

来源:Hazardous Substances Data Bank (HSDB)

代谢

替米考星，在去甲基大环内酯环和哌啶环上均标记有（14）C，通过口服给与15只雄性和15只雌性Fischer-344大鼠。剂量为每天20毫克/千克体重，连续3天。在肝脏中，放射性标记对应于替米考星和一个去甲基衍生物，T1（在大环内酯环中去甲基化）。尿液中检测到的单一放射性物质是未改变的替米考星，而在粪便中，主要的峰是母化合物，其次是较少量的去甲基替米考星和一个高分子量化合物，这种化合物已知是给药物质中的杂质，T2（由两个大环内酯环和一个哌啶环组成）。

Tilmicosin, labelled with (14)C in both the desmycosin macrolide ring and the piperidine ring, was given orally to 15 male and 15 female Fischer-344 rats. The dosage was 20 mg/kg bw per day for 3 days. In the liver, radiolabel corresponded to tilmicosin and a desmethyl derivative, T1 (demethylated in the mycaminose ring). The single radioactive substance identified in urine was unchanged tilmicosin, while in feces the major peak was parent compound with lesser amounts of desmethyl tilmicosin and a high molecular weight compound known to be present as an impurity in the administered substance, T2 (consisting of two macrolide rings and one piperidine ring).

来源:Hazardous Substances Data Bank (HSDB)

代谢

在给注射了(14)C-替米考星的结果概述中，报道称处理过的老鼠肝脏中的放射性活性轮廓与粪便中的相似。在使用高度纯化的替米考样品处理的动物中，在肝脏中未检测到代谢物T2，这表明其存在是作为药物物质组成部分直接给药的结果。肾脏中的放射性活性基本上以未改变的替米考星形式存在。

In a summary of results obtained in cattle injected with (14)C-tilmicosin, it was reported that the radioactivity profile in the liver of treated rats was similar to that in the feces. In animals treated with a highly purified sample of tilmicosin, metabolite T2 was not detected in the liver, suggesting that its presence was a result of direct administration as a component of the drug substance. Radioactivity in the kidneys was essentially in the form of unchanged tilmicosin.

来源:Hazardous Substances Data Bank (HSDB)

代谢

猪被喂食含有放射性碳-14标记的泰妙菌素的饮食，每天的剂量为400毫克，持续5天。在肝脏和肾脏中，大约60到70%的放射性标记以母药形式存在，还有少量的一级代谢物T1。同样，在尿液和粪便中，泰妙菌素的含量很高，而T1的含量很低。还检测到另一种代谢物，它构成了粪便中14%和尿液中25%的放射性活性，这种代谢物与大环内酯环中一个双键的还原然后硫酸化一致。

Pigs were fed diets containing (14)C-tilmicosin, which resulted in daily doses of 400 mg, for 5 days. Of the radiolabel in liver and kidney, approximately 60 to 70% was in the form of the parent drug and there were small amounts of T1. Similarly in urine and faeces, there were high levels of tilmicosin and low levels of T1. A further metabolite was detected that comprised 14% of faecal and 25% of urinary radioactivity and that was consistent with reduction of one double bond in the macrolide ring followed by sulfation.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

同时使用卡马西平、环孢素、地高辛、己巴比妥、苯妥英或丙戊酸与大环内酯类抗生素，已与这些药物的血药浓度升高有关；建议监测同时给药的药物的血药浓度，以避免中毒。/大环内酯类抗生素/

Concurrent use /of carbamazepine, cyclosporine, digoxin, hexobarbital, phenytoin or valproic acid/ with macrolide antibiotics has been associated with increased serum concentration of these medications; monitoring of serum concentrations of medications administered concurrently is recommended to avoid toxicity. /Macrolide antibiotics/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

黄嘌呤类药物（除二羟丙茶碱外）与macrolides（大环内酯类抗生素）同时使用可能会减少黄嘌呤类药物的肝清除率，导致血清中药物浓度升高和/或毒性增加；在与大环内酯类抗生素治疗期间和治疗后，可能需要调整黄嘌呤类药物的剂量。

Concurrent use of the xanthines (except dyphylline) with macrolides may decrease hepatic clearance of xanthines, resulting in increased serum concentrations and/or toxicity; dosage adjustment of the xanthines may be necessary during and after therapy with macrolides. /Macrolide antibiotics/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

同时使用咪达唑仑或三唑仑与macrolide类抗生素可能会降低这些药物的清除率，增加咪达唑仑或三唑仑的药理作用。/Macrolide类抗生素/

Concurrent use /of midazolam or triazolam/ with macrolide antibiotics may decrease the clearance of these medications, increasing the pharmacologic effect of midazolam or triazolam. /Macrolide antibiotics/

来源:Hazardous Substances Data Bank (HSDB)