(E)-头孢呋辛酯 | 97232-96-7

• 物质功能分类: 化学试剂 - 有机试剂 - 酯类
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 内酰胺类
• 中文名称: (E)-头孢呋辛酯
• 中文别名: 头孢呋辛酯EP杂质B
• 英文名称: trans-cefuroxime axetil
• 英文别名: anti-cefuroxime axetil；cefuroxime axetil；Ceftin；Cefuroxime axetil, (E)-；1-acetyloxyethyl (6R,7R)-3-(carbamoyloxymethyl)-7-[[(2E)-2-(furan-2-yl)-2-methoxyiminoacetyl]amino]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate
• CAS: 97232-96-7
• 化学式: C₂₀H₂₂N₄O₁₀S
• 分子量: 510.481
• InChiKey: KEJCWVGMRLCZQQ-DJMWJSSGSA-N

物化性质

• 密度：
  1.61±0.1 g/cm3(Predicted)
• 颜色/状态：
  White to almost white crystalline powder
• 溶解度：
  In water, 107 mg/L at 25 °C (est)
• 蒸汽压力：
  9.95X10-16 mm Hg at 25 °C (est)
• 稳定性/保质期：

  Stable under recommended storage conditions.

• 分解：
  When heated to decomposition it emits toxic fumes of /nitrogen oxides and sulfur oxides/.
• 碰撞截面：
  189.7 Ų [M+Na]+ [CCS Type: TW, Method: calibrated with polyalanine and drug standards]

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  35
• 可旋转键数：
  12
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  214
• 氢给体数：
  2
• 氢受体数：
  12

ADMET

代谢

口服给药后，盐酸头孢呋辛酯迅速被肠粘膜和血液中的非特异性酯酶水解为头孢呋辛；乙酸乙酯部分代谢为乙醛和醋酸。头孢呋辛不代谢，主要通过肾小球滤过和肾小管分泌以原形在尿液中排泄。

Following oral administration, cefuroxime axetil is rapidly hydrolyzed to cefuroxime by nonspecific esterases in the intestinal mucosa and blood; the axetil moiety is metabolized to acetaldehyde and acetic acid. Cefuroxime is not metabolized and is excreted unchanged principally in urine by both glomerular filtration and tubular secretion.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

降低胃酸药物可能会降低与空腹状态相比的科芬特的生物利用度，并倾向于抵消餐后吸收的效果。

Drugs that reduce gastric acidity may result in a lower bioavailability of Ceftin compared with that of fasting state and tend to cancel the effect of postprandial absorption.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

口服丙磺舒在cefuroxime给药前短暂或同时给药通常可以减缓cefuroxime的肾小管分泌速率，并产生更高、更持久的cefuroxime血药浓度。这种作用通常在治疗淋病时被利用。据报道，当丙磺舒与cefuroxime同时给药时，cefuroxime的峰浓度和药物的半衰期可增加多达30％；cefuroxime的浓度-时间曲线下面积（AUC）增加约50％。据报道，丙磺舒的联合给药还可以将cefuroxime的表观分布容积减少约20％。

Oral probenecid administered shortly before or concomitantly with cefuroxime usually slows the rate of tubular secretion of cefuroxime and produces higher and more prolonged serum concentrations of cefuroxime. This effect is usually used to therapeutic advantage in the treatment of gonorrhea. Peak serum concentrations of cefuroxime and the half-life of the drug are reportedly increased by up to 30% when probenecid is administered concomitantly; the area under the concentration-time curve (AUC) of cefuroxime is increased by about 50%. Concomitant administration of probenecid also reportedly decreases the apparent volume of distribution of cefuroxime by about 20%.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

头孢呋辛酯可能会影响肠道菌群，导致雌激素重吸收减少，从而降低含有雌激素和孕激素的口服避孕药的效果。

Cefuroxime axetil may affect gut flora, leading to decreased estrogen reabsorption and reduced efficacy of oral contraceptives containing estrogen and progestin.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

制造商表示，在接受利尿剂治疗的患者中应谨慎使用头孢呋辛，因为同时使用这些药物可能会增加不良肾脏影响的风险。

The manufacturers state that cefuroxime should be used with caution in patients receiving diuretics because concurrent use of these drugs may increase the risk of adverse renal effects.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

体外研究表明，头孢呋辛和氨基糖苷类抗生素对一些菌株（包括肠杆菌、大肠埃希菌、克雷伯菌属、奇异变形杆菌和粘质沙雷菌）的抗菌活性可能是相加的或协同的。据报道，同时使用氨基糖苷类和某些头孢菌素可能会增加治疗期间肾毒性的风险。尽管到目前为止还没有报道头孢呋辛有此效果，但如果与氨基糖苷类药物同时使用，应考虑可能会增强肾毒性的可能性。

In vitro studies indicate that the antibacterial activity of cefuroxime and aminoglycosides may be additive or synergistic against some organisms including Enterobacter, Escherichia coli, Klebsiella, Proteus mirabilis, and Serratia marcescens. Concurrent use of aminoglycosides and certain cephalosporins reportedly may increase the risk of nephrotoxicity during therapy. Although this effect has not been reported to date with cefuroxime, the possibility that nephrotoxicity may be potentiated should be considered if the drug is used concomitantly with an aminoglycoside.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

口服头孢呋辛酯后，头孢呋辛会分布到小儿中耳积液中。在一项针对1-4岁患有急性中耳炎并伴有积液的小儿的研究中，单次给予15 mg/kg剂量的头孢呋辛作为头孢呋辛酯口服悬浮液，给药后2-5小时中耳积液中的头孢呋辛浓度范围为0.2-3.6微克/毫升；同时血清中的浓度为2.8-7.3微克/毫升。

Following oral administration of cefuroxime axetil in pediatric patients with acute otitis media with effusion or with chronic or recurrent otitis media with effusion, cefuroxime is distributed into middle ear effusions. In a study in pediatric patients 1-4 years of age with acute otitis media with effusion who received a single 15 mg/kg dose of cefuroxime as cefuroxime axetil oral suspension, cefuroxime concentrations in middle ear effusions 2-5 hours after a dose ranged from 0.2-3.6 ug/mL; concurrent serum concentrations were 2.8-7.3 ug/mL.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

在儿童使用cefuroxime axetil口服悬浮液进行药代动力学研究中，药物是在餐后或与食物一起服用的；目前没有关于空腹儿童吸收悬浮液的数据。将cefuroxime axetil口服悬浮液与牛奶或乳制品同时给予3个月至12岁（平均年龄：23个月）的儿童单次10、15或20 mg/kg剂量后，大约在给药后3.6、2.7或3.1小时达到峰血清cefuroxime浓度，平均浓度分别为3.3、5.1或7 mcg/mL。

In pharmacokinetic studies of cefuroxime axetil oral suspension in children, the drug was administered postprandially or with food; no data are available regarding absorption of the suspension in fasting children. Following oral administration to children 3 months to 12 years of age (mean age: 23 months) of a single 10-, 15-, or 20-mg/kg dose of commercially available cefuroxime axetil oral suspension concomitantly with milk or milk products, peak serum cefuroxime concentrations are attained approximately 3.6, 2.7, or 3.1 hours after the dose, respectively, and average 3.3, 5.1, or 7 mcg/mL, respectively.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

研究结果表明，健康成年人服用的含125毫克/5毫升或250毫克/5毫升的cefuroxime axetil口服悬浮液具有生物等效性。在接受125毫克/5毫升或250毫克/5毫升cefuroxime axetil悬浮液250毫克剂量的健康成年人中，cefuroxime的峰血浆浓度分别为2.4或2.2毫克/毫升，且在给药后3小时达到峰值。

Results of a study in healthy adults indicate that cefuroxime axetil oral suspensions containing 125 mg/5 mL or 250 mg/5 mL are bioequivalent. In healthy adults who received a 250-mg dose of cefuroxime axetil given as a suspension containing 125 mg/5 mL or 250 mg/5 mL with food, peak plasma concentrations of cefuroxime were 2.4 or 2.2 aug/mL, respectively, and were attained 3 hours after the dose.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

口服125毫克、250毫克、500毫克或1克市售的头孢呋辛酯片剂，在成人餐后立即服用后，大约在给药后2-3小时达到头孢呋辛的峰值血清浓度，平均浓度分别为2.1、4.1、7.0或13.6微克/毫升；给药后6小时的血清浓度平均分别为0.3、0.7、2.2或3.4微克/毫升。这些人体内的药物平均药时曲线下面积（AUC）分别为6.7、12.9、27.4或50微克·小时/毫升。

Following oral administration in adults of a single 125-mg, 250-mg, 500-mg, or 1-g dose of commercially available cefuroxime axetil tablets immediately following a meal, peak serum cefuroxime concentrations are attained approximately 2-3 hours after the dose and average 2.1, 4.1, 7, or 13.6 ug/mL, respectively; serum concentrations 6 hours after the dose average 0.3, 0.7, 2.2, or 3.4 ug/mL, respectively. AUC of the drug in these individuals averaged 6.7, 12.9, 27.4, or 50 mcg-h/mL, respectively.

来源:Hazardous Substances Data Bank (HSDB)

反应信息

• 作为反应物：
  描述：

  (E)-头孢呋辛酯 以 甲醇 、 水 为溶剂， 生成 头孢呋辛酯
  参考文献：
  名称：

  头孢呋辛酯及相关化合物的光异构化动力学

  摘要：

  用HPLC研究了头孢呋辛酯水溶液在254 nm下的光致异构化动力学。总体降解是烷氧基亚氨基基团的异构化与β-内酰胺环的光解之间竞争的结果。头孢呋辛酯以两种非对映异构体的混合物形式存在，并显示出不同的反应速率。这不仅适用于光异构化步骤，而且适用于碱性条件下的基态水解。头孢呋辛酯的抗异构体及其某些降解产物也观察到了烷氧基亚氨基的光异构化。所有这些光异构化的量子产率始终低于1％，这说明了光解步骤的相对重要性。头孢呋辛酯的固定顺式与反比为1，头孢呋辛为2.1。从这项研究和以前的研究来看，与其他带有烷氧基亚氨基的抗生素相比，头孢呋辛酯在254 nm照射下最敏感。氨曲南最稳定，其次是头孢噻肟，头孢呋辛和头孢呋辛酯。

  DOI：

  10.1002/jps.2600830422
• 作为产物：
  描述：

  头孢呋辛酯 以 甲醇 、 水 为溶剂， 生成 (E)-头孢呋辛酯
  参考文献：
  名称：

  头孢呋辛酯及相关化合物的光异构化动力学

  摘要：

  用HPLC研究了头孢呋辛酯水溶液在254 nm下的光致异构化动力学。总体降解是烷氧基亚氨基基团的异构化与β-内酰胺环的光解之间竞争的结果。头孢呋辛酯以两种非对映异构体的混合物形式存在，并显示出不同的反应速率。这不仅适用于光异构化步骤，而且适用于碱性条件下的基态水解。头孢呋辛酯的抗异构体及其某些降解产物也观察到了烷氧基亚氨基的光异构化。所有这些光异构化的量子产率始终低于1％，这说明了光解步骤的相对重要性。头孢呋辛酯的固定顺式与反比为1，头孢呋辛为2.1。从这项研究和以前的研究来看，与其他带有烷氧基亚氨基的抗生素相比，头孢呋辛酯在254 nm照射下最敏感。氨曲南最稳定，其次是头孢噻肟，头孢呋辛和头孢呋辛酯。

  DOI：

  10.1002/jps.2600830422

文献信息

• SELF-ASSEMBLY OF THERAPEUTIC AGENT-PEPTIDE NANOSTRUCTURES
  申请人：Ohio State Innovation Foundation

  公开号：US20140155577A1

  公开（公告）日：2014-06-05

  Disclosed are conjugates of hydrophobic drugs linked to protected or unprotected amino acids or peptides. The disclosed conjugates are amphiphilic and can self assemble into nanotubes. Nanotubes comprising the conjugates are also described and can have high loading of the drug and protect it from degradation or elimination. The nanotubes are well suited to deliver hydrophobic and unstable drugs to individuals.

  揭示了与受保护或未受保护的氨基酸或肽连接的疏水药物的共轭物。所述的共轭物是两性的，可以自组装成纳米管。还描述了包含这些共轭物的纳米管，可以具有高药物载荷并保护药物免受降解或排泄。这些纳米管非常适合向个体输送疏水和不稳定的药物。
• Novel heterocyclic compounds, preparation process and intermediates, and use as medicaments, in particular as B-lactamase inhibitors and antibacterials
  申请人：AVENTIS PHARMA S.A.

  公开号：US20040097490A1

  公开（公告）日：2004-05-20

  The invention relates to novel heterocyclic compounds of general formula (I) and to their salts with a base or an acid: 1 The invention also relates to processes and to intermediates for the preparation of these compounds, and to their use as medicaments, in particular as antibacterials and &bgr;-lactamase inhibitors.

  这项发明涉及一般式(I)的新型杂环化合物及其与碱或酸形成的盐： 该发明还涉及制备这些化合物的过程和中间体，以及它们作为药物的用途，特别是作为抗菌药物和β-内酰胺酶抑制剂。
• [EN] COMPOUNDS (CYSTEIN BASED LIPOPEPTIDES) AND COMPOSITIONS AS TLR2 AGONISTS USED FOR TREATING INFECTIONS, INFLAMMATIONS, RESPIRATORY DISEASES ETC.<br/>[FR] COMPOSÉS (LIPOPEPTIDES À BASE DE CYSTÉINE) ET COMPOSITIONS EN TANT QU'AGONISTES DES TLR2 UTILISÉS POUR TRAITER DES INFECTIONS, INFLAMMATIONS, MALADIES RESPIRATOIRES ENTRE AUTRES
  申请人：IRM LLC

  公开号：WO2011119759A1

  公开（公告）日：2011-09-29

  The invention provides a novel class of compounds viz. generally lipopeptides like Pam3CSK4, immunogenic compositions and pharmaceutical compositions comprising such compounds and methods of using such compounds to treat or prevent diseases or disorders associated with Toll-Like Receptors 2. In one aspect, the compounds are useful as adjuvants for enhancing the effectiveness a vaccine.

  这项发明提供了一类新型化合物，即一般类似Pam3CSK4的脂肽类化合物，包括含有这类化合物的免疫原组合物和药物组合物，以及使用这类化合物治疗或预防与Toll样受体2相关的疾病或紊乱的方法。在一个方面，这些化合物可用作增强疫苗效果的佐剂。
• [EN] HETEROCYCLIC COMPOUNDS AND THEIR USE IN PREVENTING OR TREATING BACTERIAL INFECTIONS<br/>[FR] COMPOSÉS HÉTÉROCYCLIQUES ET LEUR UTILISATION DANS LA PRÉVENTION OU LE TRAITEMENT D'INFECTIONS BACTÉRIENNES
  申请人：MUTABILIS

  公开号：WO2018060481A1

  公开（公告）日：2018-04-05

  The invention relates to a compound of formula (I) and a racemate, an enantiomer, a diastereoisomer, a geometric isomer or a pharmaceutically acceptable salt thereof, and its use as antibacterial agent.

  这项发明涉及一种式(I)的化合物及其外消旋体、对映体、二对映异构体、几何异构体或药学上可接受的盐，并且其作为抗菌剂的用途。
• [EN] PROGRAMMABLE POLYMERIC DRUGS<br/>[FR] MÉDICAMENTS POLYMÈRES PROGRAMMABLES
  申请人：SONY CORP

  公开号：WO2020210689A1

  公开（公告）日：2020-10-15

  Compounds useful as biologically active compounds are disclosed. The compounds have the following structure (I): or a stereoisomer, tautomer or salt thereof, wherein R1, R2, R3, R4, R5, L, L1, L2, M and n are as defined herein. Methods associated with preparation and use of such compounds are also provided.

  披露了作为生物活性化合物有用的化合物。这些化合物具有以下结构（I）：或其立体异构体、互变异构体或盐，其中R1、R2、R3、R4、R5、L、L1、L2、M和n如本文所定义。还提供了与这些化合物的制备和使用相关的方法。