51627-14-6

• 常用中文名：头孢硫脒
• 常用英文名：Cefatrizine
• CAS号：51627-14-6
• 分子式：C₁₈H₁₈N₆O₅S₂
• 分子量：462.503
• 相关类别： 原料药 抗生素类药物 头孢菌素类药
• 发布时间：2018-02-17 08:00:00
• 更新时间：2024-01-04 17:03:30
• 【用途一】
  主要用于治疗由敏感菌所致肝胆感染、泌尿系统感染、呼吸系统感染、败血症、心内膜炎和脑膜炎等病症
• 该品为第一代头孢菌素，为中国首创用于临床。抗菌谱与头孢噻吩相似，对金葡菌、草绿色链球菌、肺炎球菌的作用较强，对肠球菌有独特的抗菌活性，主要用于金葡菌、肺炎球菌及链球菌所致呼吸道感染，胆道感染、尿路感染、妇科感染、败血症、肺炎、脑膜炎等感染。
  
  药理毒理1．药理该品对革兰阳性菌及部分阴性菌有抗菌活性，对革兰阳性球菌的作用尤强。该品体外抗菌活性试验表明：对肺炎球菌、化脓性链球菌、金黄色葡萄球菌（MSSA菌株）、表皮葡萄球菌（MSSE菌株）和卡他布兰汉菌有较强的抗菌活性，对肺炎链球菌MIC90为0.25μg/ ml，对化脓性链球菌MIC90为0.5μg/ml，对其他3种细菌的MIC90均小于8.0μg/ml，对流感嗜血杆菌亦有较强的抗菌活性，MIC90为2.0μg/ml。对肠球菌亦显示有很强的体外抗菌活性，MIC90为2.0μg/ml。对草绿色链球菌、溶血性链球菌、非溶血性链球菌、白喉杆菌、产气荚膜杆菌、破伤风杆菌和炭疽杆菌均有良好抗菌作用。对金黄色葡萄球菌（MRSA菌株）、表皮葡萄球菌（MRSE菌株）的体外抗菌活性不如万古霉素。该品作用机制为抑制敏感菌的细胞壁合成，而产生杀菌作用。2．毒理该品小鼠静脉注射的LD50为（1.02±0.04）g/kg，腹腔注射的LD50为（1.26±0.23)g/kg。生殖毒性试验中，试验组小鼠的胎仔死亡率明显高于对照组（p<0.01）。药代动力学：该品口服不吸收，静脉滴注1.0g后，血药峰浓度（Cmax)为（68.93±6.86)mg/L，血消除半衰期（t1/2β）为（1.19±0.12)h，血药浓度-时间曲线下面积（AUC)为（94.7±9.8)mg/(L.h)，12小时尿药累计排泄率为93.1±3.2%。肌内注射1.0g后，血药峰浓度（Cmax)为（35.12±4.34)mg/L，达峰时间（tmax)为（0.78±0.08)h，半衰期为（1.38±0.21)h，血药浓度-时间曲线下面积（AUC)为（85.3±8.0)mg/(L.h)，12小时尿中药累计排泄率为84.2±5.9%。与静脉滴注相比，其绝对生物利用度为90.3±6.4%。该品注射后在体内组织分布广泛，以胆汁、肝、肺等处含量为高，不透过血-脑脊液屏障。在机体内几乎不代谢，主要从尿中排出，12小时尿中排出给药量的90%以上。肾功能减退患者，肌内注射后血清半衰期延长至13.2小时，约为正常半衰期的10倍，24小时尿中仅排出给药量的3.2%，血液透析可排出给药量的20%~30%。适应症：用于敏感菌所引起呼吸系统、肝胆系统、五官、尿路感染及心内膜炎、败血症。
  用法和用量：该品口服不吸收。肌内注射：一次0.5g~1.0g,一日4次；小儿按体重一日50~100mg/kg，分3~4次给药。静脉注射：一次1g，一日2~4次；小儿按体重一日50~100mg/kg，分2~4次给药。
  临用前加灭菌注射用水或氯化钠注射液适量溶解。

名称

• 中文名: 头孢硫脒
• 英文名: Cefatrizine
• 中文别名: 7-[2-氨基-2-(4-羟基苯基)乙酰氨基]-3-(1,2,3-三唑-4-基硫)甲基-8-氧代-5-硫杂-1-氮杂二环[4.2.0]辛-2-烯-2-甲酸; 头孢曲秦; 头孢曲嗪
• 英文别名: MFCD00274172; bls640; 5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid, 7-[[2-amino-2-(4-hydroxyphenyl)acetyl]amino]-8-oxo-3-[(1H-1,2,3-triazol-4-ylthio)methyl]-; 7-{[Amino(4-hydroxyphenyl)acetyl]amino}-8-oxo-3-[(2H-1,2,3-triazol-4-ylsulfanyl)methyl]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid; antibioticbl-640; 5-Thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid, 7-[[2-amino-2-(4-hydroxyphenyl)acetyl]amino]-8-oxo-3-[(2H-1,2,3-triazol-4-ylthio)methyl]-; 7-{[amino(4-hydroxyphenyl)acetyl]amino}-8-oxo-3-[(1H-1,2,3-triazol-5-ylsulfanyl)methyl]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid; Cefatrizine; 7-{[Amino(4-hydroxyphenyl)acetyl]amino}-8-oxo-3-[(1H-1,2,3-triazol-4-ylsulfanyl)methyl]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid; EINECS 257-324-2; 5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid, 7-[[2-amino-2-(4-hydroxyphenyl)acetyl]amino]-8-oxo-3-[(1H-1,2,3-triazol-5-ylthio)methyl]-; CEPHATHIAMIDINUM; cephatriazine; s640p; Cephathiamidine; antibioticbl-s640

物化性质

• 密度: 1.7±0.1 g/cm3
• 沸点: 948.1±65.0 °C at 760 mmHg
• 分子式: C₁₈H₁₈N₆O₅S₂
• 分子量: 462.503
• 闪点: 527.2±34.3 °C
• 精确质量: 462.078003
• PSA: 225.13000
• LogP: -0.41
• 外观性状: 白色至略淡黄色粉末
• 蒸汽压: 0.0±0.3 mmHg at 25°C
• 折射率: 1.794
• 储存条件: 库房通风低温干燥

生物活性

• 描述: 头孢曲辛(BL-S-640)是一种口服活性广谱头孢菌素抗生素。头孢曲嗪也是一种eEF2K抑制剂,在人类乳腺癌细胞中具有抗增殖活性,可诱导内质网应激,导致细胞死亡。头孢曲嗪可用于癌症和细菌感染的研究[1][2]。
• 相关类别:
  信号通路 >> 细胞凋亡 >> 细胞凋亡
  研究领域 >> 癌症
  研究领域 >> 感染
  信号通路 >> 抗感染 >> 细菌
• 靶点:

  eEF2K, bacterial[1][2].

• 体外研究: 头孢曲嗪(0-100µM；24 h)以剂量依赖性方式对MCF-7和MDA-MB-436细胞生长产生显著的抗增殖作用[1]。头孢曲嗪(30µM；12 h)诱导乳腺癌细胞内质网应激[1]。头孢曲嗪(12、24、36 h)增加MCF-7和MDA-MB-436细胞中CHOP(ER应激诱导凋亡的标志物)的水平,并促进eEF2K调节的ER应激途径(Bip、p-PERK、XBP-1S和p-JNK)中核心蛋白的表达[1]。细胞增殖试验[1]细胞系：MCF-7,MDA-MB-436细胞浓度：0-100µM培养时间：24小时结果：在33µM和29µM时,对细胞产生显著的抗增殖作用,并导致MCF-7和MDA-MB-336细胞几乎50%的抑制。细胞活力测定[1]细胞系：MCF-7,MDA-MB-436细胞浓度：30µM培养时间：12小时结果：导致大量细胞质空泡化。
• 体内研究: 头孢曲嗪(BL-S-640)(0.2、1、5、25 mg/kg；口服；每天4次,连续3天)可减少奇异芽孢杆菌囊内感染模型中膀胱和肾脏中感染生物的数量[2]。动物模型：雄性Wiss Webster小鼠(19-21g；奇异芽孢杆菌囊内感染模型)[2]。剂量：0.2、1、5、25 mg/kg给药：口服；每天4次,持续3天。结果：当剂量为1 mg/kg时,膀胱中的感染微生物数量减少到1000个以下,当剂量为0.2 mg/kg时肾脏中的感染细菌数量减少到了1000个以下。

毒性和生态

CHEMICAL IDENTIFICATION RTECS NUMBER : XI0340000 CHEMICAL NAME : 5-Thia-1-azabicyclo(4.2.0)oct-2-ene-2-carboxylic acid, 7-((amino(4-hydroxyphenyl)acetyl) amino)-8-oxo-3-((1H-1,2,3-triazol-4-ylthio)methyl)-, (6R-(6-alpha,7-beta(R)))- CAS REGISTRY NUMBER : 51627-14-6 LAST UPDATED : 199410 DATA ITEMS CITED : 21 MOLECULAR FORMULA : C18-H18-N6-O5-S2 MOLECULAR WEIGHT : 462.54 WISWESSER LINE NOTATION : T46 ANV ES GUTJ CMVYZR DQ& HVQ G1S- DT5MNNJ HEALTH HAZARD DATA ACUTE TOXICITY DATA TYPE OF TEST : LD - Lethal dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE/DURATION : >6 gm/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : JJANAX Japanese Journal of Antibiotics. (Japan Antibiotics Research Assoc., 2-20-8 Kamiosaki, Shinagawa-ku, Tokyo 141, Japan) V.21- 1968- Volume(issue)/page/year: 29,612,1976 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 4325 mg/kg TOXIC EFFECTS : Behavioral - somnolence (general depressed activity) Lungs, Thorax, or Respiration - respiratory depression Skin and Appendages - hair REFERENCE : JJANAX Japanese Journal of Antibiotics. (Japan Antibiotics Research Assoc., 2-20-8 Kamiosaki, Shinagawa-ku, Tokyo 141, Japan) V.21- 1968- Volume(issue)/page/year: 29,612,1976 TYPE OF TEST : LD - Lethal dose ROUTE OF EXPOSURE : Subcutaneous SPECIES OBSERVED : Rodent - rat DOSE/DURATION : >6 gm/kg TOXIC EFFECTS : Behavioral - food intake (animal) Gastrointestinal - changes in structure or function of salivary glands REFERENCE : JJANAX Japanese Journal of Antibiotics. (Japan Antibiotics Research Assoc., 2-20-8 Kamiosaki, Shinagawa-ku, Tokyo 141, Japan) V.21- 1968- Volume(issue)/page/year: 29,612,1976 TYPE OF TEST : LD - Lethal dose ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Rodent - rat DOSE/DURATION : >240 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : JJANAX Japanese Journal of Antibiotics. (Japan Antibiotics Research Assoc., 2-20-8 Kamiosaki, Shinagawa-ku, Tokyo 141, Japan) V.21- 1968- Volume(issue)/page/year: 29,612,1976 TYPE OF TEST : LD - Lethal dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : >6 gm/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : JJANAX Japanese Journal of Antibiotics. (Japan Antibiotics Research Assoc., 2-20-8 Kamiosaki, Shinagawa-ku, Tokyo 141, Japan) V.21- 1968- Volume(issue)/page/year: 29,612,1976 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 6410 mg/kg TOXIC EFFECTS : Behavioral - somnolence (general depressed activity) Lungs, Thorax, or Respiration - respiratory depression Skin and Appendages - hair REFERENCE : JJANAX Japanese Journal of Antibiotics. (Japan Antibiotics Research Assoc., 2-20-8 Kamiosaki, Shinagawa-ku, Tokyo 141, Japan) V.21- 1968- Volume(issue)/page/year: 29,612,1976 TYPE OF TEST : LD - Lethal dose ROUTE OF EXPOSURE : Subcutaneous SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : >6 gm/kg TOXIC EFFECTS : Behavioral - food intake (animal) Gastrointestinal - changes in structure or function of salivary glands REFERENCE : JJANAX Japanese Journal of Antibiotics. (Japan Antibiotics Research Assoc., 2-20-8 Kamiosaki, Shinagawa-ku, Tokyo 141, Japan) V.21- 1968- Volume(issue)/page/year: 29,612,1976 TYPE OF TEST : LD - Lethal dose ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : >400 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : JJANAX Japanese Journal of Antibiotics. (Japan Antibiotics Research Assoc., 2-20-8 Kamiosaki, Shinagawa-ku, Tokyo 141, Japan) V.21- 1968- Volume(issue)/page/year: 29,612,1976 TYPE OF TEST : LD - Lethal dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Mammal - dog DOSE/DURATION : >1600 mg/kg TOXIC EFFECTS : Gastrointestinal - nausea or vomiting REFERENCE : JJANAX Japanese Journal of Antibiotics. (Japan Antibiotics Research Assoc., 2-20-8 Kamiosaki, Shinagawa-ku, Tokyo 141, Japan) V.21- 1968- Volume(issue)/page/year: 29,612,1976 TYPE OF TEST : LD - Lethal dose ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Mammal - dog DOSE/DURATION : >3 gm/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : JJANAX Japanese Journal of Antibiotics. (Japan Antibiotics Research Assoc., 2-20-8 Kamiosaki, Shinagawa-ku, Tokyo 141, Japan) V.21- 1968- Volume(issue)/page/year: 29,612,1976 TYPE OF TEST : LD - Lethal dose ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Mammal - dog DOSE/DURATION : >40 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : JJANAX Japanese Journal of Antibiotics. (Japan Antibiotics Research Assoc., 2-20-8 Kamiosaki, Shinagawa-ku, Tokyo 141, Japan) V.21- 1968- Volume(issue)/page/year: 29,612,1976 TYPE OF TEST : LD - Lethal dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rabbit DOSE/DURATION : >5 gm/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : JJANAX Japanese Journal of Antibiotics. (Japan Antibiotics Research Assoc., 2-20-8 Kamiosaki, Shinagawa-ku, Tokyo 141, Japan) V.21- 1968- Volume(issue)/page/year: 29,612,1976 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - rabbit DOSE/DURATION : 1500 mg/kg TOXIC EFFECTS : Behavioral - somnolence (general depressed activity) Lungs, Thorax, or Respiration - respiratory depression Skin and Appendages - hair REFERENCE : JJANAX Japanese Journal of Antibiotics. (Japan Antibiotics Research Assoc., 2-20-8 Kamiosaki, Shinagawa-ku, Tokyo 141, Japan) V.21- 1968- Volume(issue)/page/year: 29,612,1976 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Subcutaneous SPECIES OBSERVED : Rodent - rabbit DOSE/DURATION : 3 gm/kg TOXIC EFFECTS : Behavioral - food intake (animal) Gastrointestinal - hypermotility, diarrhea REFERENCE : JJANAX Japanese Journal of Antibiotics. (Japan Antibiotics Research Assoc., 2-20-8 Kamiosaki, Shinagawa-ku, Tokyo 141, Japan) V.21- 1968- Volume(issue)/page/year: 29,612,1976 TYPE OF TEST : LD - Lethal dose ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Rodent - rabbit DOSE/DURATION : >80 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : JJANAX Japanese Journal of Antibiotics. (Japan Antibiotics Research Assoc., 2-20-8 Kamiosaki, Shinagawa-ku, Tokyo 141, Japan) V.21- 1968- Volume(issue)/page/year: 29,612,1976 ** REPRODUCTIVE DATA ** TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral DOSE : 175 mg/kg SEX/DURATION : female 8-14 day(s) after conception TOXIC EFFECTS : Reproductive - Specific Developmental Abnormalities - musculoskeletal system Reproductive - Effects on Newborn - growth statistics (e.g.%, reduced weight gain) REFERENCE : JJANAX Japanese Journal of Antibiotics. (Japan Antibiotics Research Assoc., 2-20-8 Kamiosaki, Shinagawa-ku, Tokyo 141, Japan) V.21- 1968- Volume(issue)/page/year: 29,129,1976 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral DOSE : 2800 mg/kg SEX/DURATION : female 8-14 day(s) after conception TOXIC EFFECTS : Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus) REFERENCE : JJANAX Japanese Journal of Antibiotics. (Japan Antibiotics Research Assoc., 2-20-8 Kamiosaki, Shinagawa-ku, Tokyo 141, Japan) V.21- 1968- Volume(issue)/page/year: 29,129,1976 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral DOSE : 5600 mg/kg SEX/DURATION : female 8-14 day(s) after conception TOXIC EFFECTS : Reproductive - Effects on Embryo or Fetus - fetal death REFERENCE : JJANAX Japanese Journal of Antibiotics. (Japan Antibiotics Research Assoc., 2-20-8 Kamiosaki, Shinagawa-ku, Tokyo 141, Japan) V.21- 1968- Volume(issue)/page/year: 29,129,1976 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral DOSE : 175 mg/kg SEX/DURATION : female 7-13 day(s) after conception TOXIC EFFECTS : Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus) Reproductive - Specific Developmental Abnormalities - musculoskeletal system REFERENCE : JJANAX Japanese Journal of Antibiotics. (Japan Antibiotics Research Assoc., 2-20-8 Kamiosaki, Shinagawa-ku, Tokyo 141, Japan) V.21- 1968- Volume(issue)/page/year: 29,129,1976 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral DOSE : 225 mg/kg SEX/DURATION : female 8-16 day(s) after conception TOXIC EFFECTS : Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus) Reproductive - Specific Developmental Abnormalities - musculoskeletal system REFERENCE : JJANAX Japanese Journal of Antibiotics. (Japan Antibiotics Research Assoc., 2-20-8 Kamiosaki, Shinagawa-ku, Tokyo 141, Japan) V.21- 1968- Volume(issue)/page/year: 29,144,1976 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral DOSE : 3600 mg/kg SEX/DURATION : female 8-16 day(s) after conception TOXIC EFFECTS : Reproductive - Effects on Embryo or Fetus - fetal death REFERENCE : JJANAX Japanese Journal of Antibiotics. (Japan Antibiotics Research Assoc., 2-20-8 Kamiosaki, Shinagawa-ku, Tokyo 141, Japan) V.21- 1968- Volume(issue)/page/year: 29,144,1976