(4R)-3-[(3S,5S)-5-(dimethylcarbamoyl)pyrrolidin-3-yl]sulfanyl-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-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: (4R)-3-[(3S,5S)-5-(dimethylcarbamoyl)pyrrolidin-3-yl]sulfanyl-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid
• 化学式: C₁₇H₂₅N₃O₅S
• 分子量: 383.5
• InChiKey: DMJNNHOOLUXYBV-WFEXRQQUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -2.4
• 重原子数：
  26
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  136
• 氢给体数：
  3
• 氢受体数：
  7

ADMET

代谢

美罗培南有一个微生物学上不活跃的代谢物。

There is one metabolite of meropenem that is microbiologically inactive.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

文献中的病例报告显示，将包括美罗培南在内的碳青霉烯类药物与服用丙戊酸或二丙戊酸钠的患者联合使用，会导致丙戊酸浓度降低。由于这种相互作用，丙戊酸浓度可能会降至治疗范围以下，从而增加突破性癫痫发作的风险。尽管这种相互作用的机制尚不清楚，但体外和动物研究的数据表明，碳青霉烯类药物可能抑制丙戊酸葡萄糖醛酸代谢物（VPA-g）水解回丙戊酸的过程，从而降低丙戊酸的血清浓度。如果需要使用注射用美罗培南，那么应考虑补充抗惊厥治疗。

Case reports in the literature have shown that co-administration of carbapenems, including meropenem, to patients receiving valproic acid or divalproex sodium results in a reduction in valproic acid concentrations. The valproic acid concentrations may drop below the therapeutic range as a result of this interaction, therefore increasing the risk of breakthrough seizures. Although the mechanism of this interaction is unknown, data from in vitro and animal studies suggest that carbapenems may inhibit the hydrolysis of valproic acid's glucuronide metabolite (VPA-g) back to valproic acid, thus decreasing the serum concentrations of valproic acid. If administration of Meropenem for injection is necessary, then supplemental anti-convulsant therapy should be considered

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

普罗布考与美罗培南竞争活性肾小管分泌，导致美罗培南的血药浓度升高。不建议将普罗布考与美罗培南联合使用。

Probenecid competes with meropenem for active tubular secretion, resulting in increased plasma concentrations of meropenem. Co-administration of probenecid with meropenem is not recommended.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 解毒与急救

/SRP:/ 立即急救：确保已经进行了充分的中和。如果患者停止呼吸，请开始人工呼吸，最好使用需求阀复苏器、球囊阀面罩设备或口袋面罩，按训练操作。如有必要，执行心肺复苏。立即用缓慢流动的水冲洗受污染的眼睛。不要催吐。如果发生呕吐，让患者前倾或置于左侧（如果可能的话，头部向下）以保持呼吸道畅通，防止吸入。保持患者安静，维持正常体温。寻求医疗帮助。 /毒物A和B/

/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/

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。观察呼吸不足的迹象，如有需要，辅助通气。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。在运输过程中，用0.9%的生理盐水（NS）连续冲洗每只眼睛……。不要使用催吐剂。对于摄入，如果患者能够吞咽，有强烈的咳嗽反射，并且不流口水，冲洗口腔并给予5毫升/千克，最多200毫升的水进行稀释……。在去污染后，用干燥的无菌敷料覆盖皮肤烧伤……。/毒物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"，最小流量/。如果出现低血容量的迹象，使用0.9%生理盐水（NS）或乳酸林格氏液。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……。/Poisons A and 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)

吸收、分配和排泄

大约70%的静脉给药剂量在12小时内以未改变的厄他培南形式在尿液中回收，此后很少能检测到进一步的尿液排泄。在500毫克剂量给药后，厄他培南在尿液中的浓度超过10微克/毫升可维持长达5小时。

Approximately 70% of the intravenously administered dose is recovered as unchanged meropenem in the urine over 12 hours, after which little further urinary excretion is detectable. Urinary concentrations of meropenem in excess of 10 ug/mL are maintained for up to 5 hours after a 500 mg dose.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

美罗培南分布到大多数身体组织和体液中，包括支气管粘膜、肺、胆汁、妇科组织（子宫内膜、子宫肌层、卵巢、宫颈、输卵管）、肌肉、心脏瓣膜、皮肤、间质和腹膜液以及脑脊液。血浆蛋白结合率大约为2%。该药物部分代谢至少产生一个微生物学上无活性的代谢物。大约70%的静脉注射剂量以原药形式通过肾小管分泌和肾小球滤过作用随尿液排出。

Meropenem is distributed into most body tissues and fluids, including bronchial mucosa, lung, bile, gynecologic tissue (endometrium, myometrium, ovary, cervix, fallopian tube), muscle, heart valves, skin, interstitial and peritoneal fluid, and CSF. Plasma protein binding is approximately 2%. The drug is partially metabolized to at least one microbiologically inactive metabolite. About 70% of an IV dose is eliminated in urine as unchanged drug by tubular secretion and glomerular filtration.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

在健康志愿者中，单次静脉输注美罗培南注射液（IV）30分钟后，500毫克剂量的平均血浆峰浓度约为23微克/毫升（范围14-26），1克剂量的平均血浆峰浓度约为49微克/毫升（范围39-58）。健康志愿者通过5分钟静脉推注美罗培南注射液（IV），500毫克剂量的平均血浆峰浓度约为45微克/毫升（范围18-65），1克剂量的平均血浆峰浓度约为112微克/毫升（范围83-140）。在静脉注射500毫克剂量后，美罗培南的平均血浆浓度通常在给药后6小时降至大约1微克/毫升。在使用500毫克每8小时一次或1克每6小时一次的给药方案的健康志愿者中，没有观察到美罗培南在血浆中的累积。

At the end of a 30 minute intravenous infusion of a single dose of Meropenem for injection (IV) in healthy volunteers, mean peak plasma concentrations of meropenem are approximately 23 ug/mL (range 14-26) for the 500 mg dose and 49 ug/mL (range 39-58) for the 1 g dose. A 5-minute intravenous bolus injection of Meropenem for injection (IV) in healthy volunteers results in mean peak plasma concentrations of approximately 45 ug/mL (range 18-65) for the 500 mg dose and 112 ug/mL (range 83-140) for the 1 g dose. Following intravenous doses of 500 mg, mean plasma concentrations of meropenem usually decline to approximately 1 ug/mL at 6 hours after administration. No accumulation of meropenem in plasma was observed with regimens using 500 mg administered every 8 hours or 1 g administered every 6 hours in healthy volunteers with normal renal function.

来源:Hazardous Substances Data Bank (HSDB)

文献信息

• Process for The Preparation of Beta-Lactam Antibiotic
  申请人：Surulichamy Senthilkumar

  公开号：US20090264643A1

  公开（公告）日：2009-10-22

  The present invention relates to a process for the preparation of Meropenem of formula (I) in sterile form and also provides an improved process for the preparation of compound of formula (V), which is an important intermediate in the synthesis of Meropenem.

  本发明涉及一种无菌形式的公式（I）美罗培南的制备过程，并提供了一种改进的公式（V）化合物的制备过程，该化合物是美罗培南合成中的一个重要中间体。
• PROCESS FOR THE PREPARATION OF BETA-LACTAM ANTIBIOTIC
  申请人：SURULICHAMY Senthilkumar

  公开号：US20120095210A1

  公开（公告）日：2012-04-19

  The present invention provides a novel process for the preparation of the meropenem trihydrate of formula (I).

  本发明提供了一种制备化学式（I）的美罗培南三水合物的新工艺。
• US8148520B2
  申请人：——

  公开号：US8148520B2

  公开（公告）日：2012-04-03
• [EN] AN IMPROVED PROCESS FOR THE PREPARATION OF BETA-LACTAM ANTIBIOTIC<br/>[FR] PROCEDE AMELIORE DE PREPARATION D'UN ANTIBIOTIQUE BETA-LACTAME
  申请人：ORCHID CHEMICALS & PHARM LTD

  公开号：WO2007031858A2

  公开（公告）日：2007-03-22

  [EN] The present invention relates to a process for the preparation of Meropenem of formula (I) in sterile form and also provides an improved process for the preparation of compound of formula (V), which is an important intermediate in the synthesis of Meropenem.
  [FR] La présente invention se rapporte à un procédé permettant de préparer du méropénème représenté par la formule (I) sous forme stérile, et a également trait à un procédé amélioré permettant de préparer un composé représenté par la formule (V), qui est un intermédiaire important dans la synthèse de méropénème.