(7R)-7-[[(2E)-2-(2-amino-1,3-thiazol-4-yl)-2-methoxyiminoacetyl]amino]-3-(furan-2-carbonylsulfanylmethyl)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 内酰胺类
• 英文名称: (7R)-7-[[(2E)-2-(2-amino-1,3-thiazol-4-yl)-2-methoxyiminoacetyl]amino]-3-(furan-2-carbonylsulfanylmethyl)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid
• 化学式: C₁₉H₁₇N₅O₇S₃
• 分子量: 523.6
• InChiKey: ZBHXIWJRIFEVQY-YLBYDCGLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.2
• 重原子数：
  34
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  256
• 氢给体数：
  3
• 氢受体数：
  13

ADMET

代谢

对4只雄性和4只雌性Sprague-Dawley大鼠肌肉注射(14)C-头孢噻呋（2毫克/千克体重）的研究发现，给药剂量的55%通过尿液排出，大约30%通过胃肠道和粪便排出。主要的尿液代谢物是脱氧酰头孢噻呋（DFC）。头孢噻呋的代谢在通过肌肉注射途径给予(14)C-头孢噻呋（2毫克/千克体重）的小牛中相似。未代谢的头孢噻呋也存在于尿液中（总放射活性的4.4-21%）。

A study of 4 male and 4 female Sprague-Dawley rats treated intramuscularly with (14)C-ceftiofur (2 mg/kg bw) revealed that 55% of the administered dose was excreted in the urine and about 30% in the GI tract and faeces. The major urinary metabolite was desfuroylceftiofur (DFC). The metabolism of ceftiofur was similar in calves administered (14)C-ceftiofur (2 mg/kg bw) via the i.m. route. Unmetabolized ceftiofur was also present in the urine (4.4-21% of total radioactivity).

来源:Hazardous Substances Data Bank (HSDB)

代谢

在一项与牛进行的比较研究中，一组Sprague-Dawley大鼠（每性别7只）接受了单次口服剂量的(14)C-头孢噻呋（200 mg/kg体重）。大约55%的总剂量在尿液中回收，其余部分存在于粪便和胃肠道中。...主要的尿液代谢物是头孢噻呋砜胱氨酸硫酯。

A group of Sprague-Dawley rats (7/sex) received single oral doses of (14)C-ceftiofur (200 mg/kg bw) in a comparative study with calves. Approximately 55% of the total dose was recovered in the urine and the rest was present in the feces and GI tract. ... The major urinary metabolite was ceftiofursulfoxide cysteine thioester.

来源:Hazardous Substances Data Bank (HSDB)

代谢

HPLC分析由aro氯诱导的大鼠肝脏S-9部分在体外形成的(14)C-头孢噻呋代谢物，结果显示脱氧头孢噻呋是主要的代谢物。低剂量(119 mg/kg bw)的头孢噻呋在15分钟内被完全代谢。较高剂量(857 mg/kg bw)在孵化60分钟后转化为脱氧头孢噻呋。

HPLC analysis of metabolites of (14)C-ceftiofur formed by arochlor-induced rat liver S-9 fractions in vitro revealed that desfuroylceftiofur was the major metabolite. Low doses (119 mg/kg bw) of ceftiofur were completely metabolized within 15 minutes. Higher doses (857 mg/kg bw) were converted to desfuroylceftiofur after 60 minutes of incubation.

来源:Hazardous Substances Data Bank (HSDB)

代谢

在一项研究中，对8周大的Sprague-Dawley大鼠（每性7只）通过口服灌胃方式给予（14）C-头孢噻呋（800 mg/kg体重/天）连续5天，发现了几种尿液代谢物，包括去酰基头孢噻呋、头孢噻呋亚砜和胱氨酸二硫键。

A study in 8-week old Sprague-Dawley rats (7/sex) treated with (14)C-ceftiofur (800 mg/kg bw/day) by oral gavage for 5 days revealed several urinary metabolites, including desfuroylceftiofur, ceftiofur sulfoxide, and cysteine disulfide.

来源:Hazardous Substances Data Bank (HSDB)

代谢

对2只雄性大鼠进行了一项研究，这些大鼠接受了一次肌内注射(14)C-头孢噻呋，研究发现去氧甲酰头孢噻呋以与主要血清蛋白（白蛋白和α-1-抗胰蛋白酶）的巯基结合的复合物形式存在。

A study of 2 male rats treated with a single i.m. injection of (14)C-ceftiofur revealed that desfuroylceftiofur existed as complexes bound by sulfhydryl groups to major serum proteins, albumin and alpha-1- antitrypsin.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 解毒与急救

/SRP:/ 基本治疗：建立专利气道（如有需要，使用口咽或鼻咽气道）。如有必要，进行吸痰。密切观察呼吸不足的迹象，如有需要，协助通气。通过非循环呼吸面罩以10至15升/分钟的速度给予氧气。监测肺水肿，如有必要，进行治疗……。监测休克，如有必要，进行治疗……。预防癫痫发作，如有必要，进行治疗……。对于眼睛污染，立即用水冲洗眼睛。在转运过程中，用0.9%的生理盐水（NS）持续冲洗每只眼睛……。不要使用催吐剂。对于摄入，如果患者能吞咽、有强烈的干呕反射且不流口水，则用温水冲洗口腔，并给予5毫升/千克，最多200毫升的水进行稀释……。在去污后，用干燥的无菌敷料覆盖皮肤烧伤……。/毒药A和B/

/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 ml/kg up to 200 ml of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 解毒与急救

/SRP:/ 高级治疗：对于无意识、严重肺水肿或严重呼吸困难的病人，考虑进行口咽或鼻咽气管插管以控制气道。使用气囊面罩装置的正压通气技术可能有益。考虑使用药物治疗肺水肿...。对于严重的支气管痉挛，考虑给予β激动剂，如沙丁胺醇...。监测心率和必要时治疗心律失常...。开始静脉输注5%葡萄糖水（D5W）/SRP: "保持开放"，最低流量/。如果出现低血容量的迹象，使用0.9%盐水（NS）或乳酸钠林格氏液。对于伴有低血容量迹象的低血压，谨慎给予液体。注意液体过载的迹象...。用地西泮或劳拉西泮治疗癫痫...。使用丙美卡因氢氯化物协助眼部冲洗...。/毒物A和B/

/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 非人类毒性摘录

实验室动物：急性暴露/ 在一项吸入研究中，将头孢喹夫以8.3毫克/升的气溶胶浓度给药给一组5只雄性和5只雌性Sprague-Dawley大鼠，暴露时间为4小时。在暴露期间，大鼠表现出流涎、鼻涕和呼吸困难；这些症状在暴露后1小时内几乎消失。暴露后的症状包括6只大鼠腹泻，1只大鼠鼻孔周围有红色结痂物质。大体和显微镜检查没有发现任何与治疗相关的变化。[联合FAO/WHO食品添加剂专家委员会；WHO食品添加剂系列36：某些兽药残留食品中毒理学评估：头孢喹夫（1996年）。截至2006年7月17日，可从以下网址获得：http://www.inchem.org/documents/jecfa/jecmono/v36je01.htm]

/LABORATORY ANIMALS: Acute Exposure/ In an inhalation study, ceftiofur was administered at an aerosol concentration of 8.3 mg/L to a group of 5 male and 5 female Sprague-Dawley rats for a 4-hr exposure period. During exposure, rats exhibited salivation, nasal discharge and dyspnea; these signs virtually disappeared within 1 hr after exposure. Post-exposure signs included diarrhea in 6 rats, and 1 rat exhibited a red encrusted material around the nares. Both gross and microscopic examination did not reveal any treatment-related changes.[Joint FAO/WHO Expert Committee on Food Additives; WHO Food Additive Series 36: Toxicological Evaluation of Certain Veterinary Drug Residues in Food: Ceftiofur (1996). Available from, as of July 17, 2006: http://www.inchem.org/documents/jecfa/jecmono/v36je01.htm]

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 非人类毒性摘录

实验室动物：急性暴露/在急性口服研究中，将头孢噻呋以单次剂量最高7800毫克/千克体重给药给Sprague-Dawley大鼠（每组10只/性别）。在两个最高剂量水平上观察到与治疗相关的腹泻。没有观察到其他与治疗相关的体征。[联合国粮农组织/世界卫生组织食品添加剂专家联合委员会；世界卫生组织食品添加剂系列36：某些兽药残留食品中毒理学的评估：头孢噻呋（1996年）。截至2006年7月17日，可从以下网址获得：http://www.inchem.org/documents/jecfa/jecmono/v36je01.htm]

/LABORATORY ANIMALS: Acute Exposure/ In an acute oral study, ceftiofur was administered as a single dose of up to 7800 mg/kg bw to groups of Sprague-Dawley rats (10/sex). Treatment-related diarrhea was noted at the 2 highest dose levels. No other treatment-related signs were observed.[Joint FAO/WHO Expert Committee on Food Additives; WHO Food Additive Series 36: Toxicological Evaluation of Certain Veterinary Drug Residues in Food: Ceftiofur (1996). Available from, as of July 17, 2006: http://www.inchem.org/documents/jecfa/jecmono/v36je01.htm]

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 非人类毒性摘录

实验动物：急性暴露/ 在对牛每天肌肉注射高达55毫克/千克体重/天，连续5天，以及对猪每天肌肉注射高达125毫克/千克体重/天，连续5天的研究中，最显著的发现是短暂的注射部位反应。[欧洲药品管理局（EMA），欧洲药品评估机构，兽药评估单位，兽药产品委员会；头孢噻夫，摘要报告（2）。EMA/MRL/498/98-最终（1999年7月）。截至2006年7月21日，可从以下网址获得：http://www.ema.europa.eu/ema/index.jsp?curl=pages/document_library/landing/document_library_search.jsp&murl=menus/document_library/document_library.jsp&mid]

/LABORATORY ANIMALS: Acute Exposure/ In studies in which cattle were given daily intramuscular injections of up to 55 mg/kg bw/day for 5 days and pigs were given dally intramuscular injections of up to 125 mg/kg bw/day for 5 days, transient injection site reactions were the most notable findings.[European Medicines Agency (EMEA), The European Agency for the Evaluation of Medicinal Products, Veterinary Medicines Evaluation Unit, Committee for Veterinary Medicinal Products; Ceftiofur, Summary Report (2). EMEA/MRL/498/98-Final (July 1999). Available from, as of July 21, 2006: http://www.ema.europa.eu/ema/index.jsp?curl=pages/document_library/landing/document_library_search.jsp&murl=menus/document_library/document_library.jsp&mid]

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

对4只雄性和4只雌性Sprague-Dawley大鼠进行肌肉注射(14)C-头孢噻呋（2 mg/kg 体重）的研究发现，给药剂量的55%通过尿液排出，大约30%通过胃肠道和粪便排出。主要的尿液代谢物是去戊酰头孢噻呋（DFC）。头孢噻呋的代谢在通过肌肉注射途径给药的犊牛中相似。未代谢的头孢噻呋也存在于尿液中（总放射活性的4.4-21%）。

A study of 4 male and 4 female Sprague-Dawley rats treated intramuscularly with (14)C-ceftiofur (2 mg/kg bw) revealed that 55% of the administered dose was excreted in the urine and about 30% in the GI tract and feces. The major urinary metabolite was desfuroylceftiofur (DFC). The metabolism of ceftiofur was similar in calves administered (14)C-ceftiofur (2 mg/kg bw) via the i.m. route. Unmetabolized ceftiofur was also present in the urine (4.4-21% of total radioactivity).

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

在一项与牛的比较研究中，一组Sprague-Dawley大鼠（每性别7只）接受了单次口服剂量的(14)C-头孢噻呋（200 mg/kg体重）。大约55%的总剂量在尿液中回收，其余存在于粪便和胃肠道中。6小时时的血浆浓度为1 mg/kg，所有组织中（即肝脏、肌肉和脂肪）都存在微量的头孢噻呋。残留水平最高（0.7 mg/kg）的部位在肾脏。

A group of Sprague-Dawley rats (7/sex) received single oral doses of (14)C-ceftiofur (200 mg/kg bw) in a comparative study with calves. Approximately 55% of the total dose was recovered in the urine and the rest was present in the feces and GI tract. Plasma concentration at 6 hr was 1 mg/kg and trace amounts of ceftiofur were present in all tissues (i.e. liver, muscle and fat). The highest residue levels (0.7 mg/kg) were present in kidney.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

对泌乳期奶牛使用(14)C-头孢噻呋（2.3 mg/kg 体重/天，连续5天）进行研究，结果显示32-38%的放射性物质以自由代谢物的形式存在于牛奶中。主要的代谢物是脱脲基头孢噻呋半胱氨酸二硫化物，占总放射性的7-9%。牛奶中没有检测到母体化合物。

A study of lactating cows treated with (14)C-ceftiofur (2.3 mg/kg bw/day for 5 days) revealed that 32-38% of the radioactivity was present in the milk as free metabolites. The major metabolite was desfuroylceftiofur cysteine disulfide representing 7-9% of the total radioactivity. No parent compound was detected in the milk.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

一项关于给公牛静脉注射(14)C-头孢噻呋的研究显示，给药剂量的55%通过尿液排出，大约30%通过消化道和粪便排出。尿液和血浆中的初始代谢物是去甲酰头孢噻呋。放射性代谢物的高效液相色谱分析结果与大鼠研究的结果相似。产生了一系列代谢物，主要代谢物（占尿液代谢物总量的87%）是去甲酰头孢噻呋乙酰胺结合物。尿液中没有观察到母体化合物。

A study of im administration of (14)C-ceftiofur in a bull revealed that 55% of the administered dose was excreted in the urine and approximately 30% in the GI tract and feces. The initial metabolite in both urine and plasma was desfuroylceftiofur. HPLC analysis of radioactive metabolites was similar to the results found in the rat studies. A number of metabolites were produced, the major metabolite (87% of total urinary metabolites) being desfuroylceftiofur acetamide conjugates. No parent compound was observed in the urine.

来源:Hazardous Substances Data Bank (HSDB)