N-{2-氯-1-[3,4,5-三羟基-6-（甲基硫烷基）恶烷-2-基]丙基}-1-甲基-4-丙基吡咯烷-2-羧酰胺 | 1097774-72-5

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 中文名称: N-{2-氯-1-[3,4,5-三羟基-6-（甲基硫烷基）恶烷-2-基]丙基}-1-甲基-4-丙基吡咯烷-2-羧酰胺
• 英文名称: N-{2-chloro-1-[3,4,5-trihydroxy-6-(methylsulfanyl)oxan-2-yl]propyl}-1-methyl-4-propylpyrrolidine-2-carboxamide
• 英文别名: N-[2-chloro-1-(3,4,5-trihydroxy-6-methylsulfanyloxan-2-yl)propyl]-1-methyl-4-propylpyrrolidine-2-carboxamide
• CAS: 1097774-72-5
• 化学式: C₁₈H₃₃ClN₂O₅S
• mdl: MFCD03253991
• 分子量: 425.0
• InChiKey: KDLRVYVGXIQJDK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  27
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.944
• 拓扑面积：
  128
• 氢给体数：
  4
• 氢受体数：
  7

ADMET

代谢

克林霉素部分代谢为生物活性和非活性代谢物。主要的生物活性代谢物是克林霉素亚砜和N-去甲基克林霉素，它们通过尿液、胆汁和粪便排出。在24小时内，大约10%的口服克林霉素剂量以活性药物和代谢物的形式通过尿液排出，3.6%通过粪便排出；其余以非活性代谢物的形式排出。

Clindamycin is partially metabolized to bioactive and inactive metabolites. The major bioactive metabolites are clindamycin sulfoxide and N-demethyl-clindamycin which are excreted in urine, bile, and feces. Within 24 hours, approximately 10% of an oral dose of clindamycin is excreted in urine and 3.6% is excreted in feces as active drug and metabolites; the remainder is excreted as inactive metabolites.

来源:Hazardous Substances Data Bank (HSDB)

代谢

大约10%的克林霉素以原形从尿液中排出，少量在粪便中可以发现...克林霉素通过代谢转化为N-去甲基克林霉素和克林霉素亚砜，这些代谢物在尿液和胆汁中排出。

Only about 10% of the clindamycin admin is excreted unaltered in urine, and small quantities are found in feces ... Clindamycin is inactivated by metabolism to N-demethylclindamycin and clindamycin sulfoxide, which are excreted in the urine and bile.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 肝毒性

克林霉素与两种形式的肝毒性有关：短暂血清转氨酶升高通常在连续几天高剂量静脉给药后发生；以及，在开始治疗1到3周内出现的急性特异质性肝损伤，通常是轻微且自限性的。 高剂量的静脉注射克林霉素可能会在治疗5到15天后伴随血清ALT水平升高，升高范围是正常上限的2到10倍，这与静脉注射苯唑西林治疗时发生的情况相似（案例1）。如果出现症状、黄疸和碱性磷酸酶升高，都较为轻微（案例2），并且在停止克林霉素或转为较低剂量或口服制剂（这种情况很少发生）后，转氨酶水平会迅速降至正常范围（1到2周内）。 克林霉素治疗还与在开始口服或静脉治疗1到3周后出现的临床明显特异质性肝损伤有关（案例3）。血清酶升高的模式通常是肝细胞型或混合型，但也可能是胆汁淤积型。过敏表现如皮疹、发热和嗜酸性粒细胞增多是典型的，但通常不显著，并非所有病例都有。自身抗体通常不存在。急性肝损伤可能伴随其他超敏反应的迹象，如史蒂文斯-约翰逊综合征或其他严重皮肤反应。肝损伤通常为轻中度，停药后迅速缓解。然而，也有致命案例的报道。 可能性评分：B（高度可能是临床明显肝损伤的原因）。

Clindamycin has been linked to two forms of hepatotoxicity: transient serum aminotransferase elevations usually occurring after several days of high intravenous doses; and, an acute, idiosyncratic liver injury that arises within 1 to 3 weeks of starting therapy and is typically mild and self-limited. High doses of intravenous clindamycin can be accompanied by elevations in serum ALT levels in the range of 2 to 10 times the upper limit of normal starting after 5 to 15 days of therapy in a manner similar to what occurs with intravenous oxacillin therapy (Case 1). Symptoms, jaundice, and alkaline phosphatase elevations are mild if they occur at all (Case 2), and aminotransferase levels rapidly fall into the normal range (in 1 to 2 weeks) upon stopping clindamycin or switching to lower doses or to oral formulations with which it rarely occurs. Clindamycin therapy has also been linked to a clinically apparent, idiosyncratic liver injury that arises between 1 to 3 weeks after starting either oral or parenteral therapy (Case 3). The pattern of serum enzyme elevations is typically hepatocellular or mixed, but can be cholestatic. Allergic manifestations such as rash, fever and eosinophilia are typical, but often are not prominent and are not present in all cases. Autoantibodies are generally not present. The acute liver injury may accompany other signs of hypersensitivity such as Stevens Johnson syndrome or other severe skin reactions. The liver injury is usually mild-to-moderate in severity and resolves rapidly with stopping. However, fatal instances have been reported. Likelihood score: B (highly likely cause of clinically apparent liver injury).

来源:LiverTox

毒理性

• 在妊娠和哺乳期间的影响

◉ 母乳喂养期间使用总结：克林霉素可能会对哺乳婴儿的胃肠道菌群产生不利影响。如果哺乳母亲需要口服或静脉注射克林霉素，这并不是停止哺乳的理由，但可以选择其他药物。监测婴儿可能的胃肠道菌群影响，如腹泻、念珠菌病（鹅口疮、尿布疹）或罕见的情况下，血便提示可能的抗生素相关性结肠炎。 阴道给药不太可能引起婴儿副作用，尽管大约30%的阴道剂量会被吸收。对于痤疮的局部给药，婴儿副作用不太可能发生；然而，如果被婴儿摄入，乳房上的局部应用可能会增加腹泻的风险。只有水溶性乳膏、泡沫、凝胶或液体产品应涂抹在乳房上，因为软膏可能会让婴儿通过舔食接触到高水平的矿物石蜡。 ◉ 对哺乳婴儿的影响：一名5天大的哺乳婴儿出现血便，可能是由于母亲同时静脉注射克林霉素600毫克，每6小时一次，以及庆大霉素80毫克，每8小时一次。据报道，婴儿的大便具有正常菌群，在停止哺乳24小时后大便变成了便隐血阴性。在停止母亲抗生素的第六天，婴儿在恢复哺乳后没有遇到进一步的困难。 ◉ 对泌乳和母乳的影响：截至修订日期，没有找到相关的已发布信息。

◉ Summary of Use during Lactation:Clindamycin has the potential to cause adverse effects on the breastfed infant's gastrointestinal flora. If oral or intravenous clindamycin is required by a nursing mother, it is not a reason to discontinue breastfeeding, but an alternate drug may be preferred. Monitor the infant for possible effects on the gastrointestinal flora, such as diarrhea, candidiasis (thrush, diaper rash) or rarely, blood in the stool indicating possible antibiotic-associated colitis. Vaginal application is unlikely to cause infant side effects, although about 30% of a vaginal dose is absorbed. Infant side effects are unlikely with topical administration for acne; however, topical application to the breast may increase the risk of diarrhea if it is ingested by the infant. Only water-miscible cream, foam, gel or liquid products should be applied to the breast because ointments may expose the infant to high levels of mineral paraffins via licking. ◉ Effects in Breastfed Infants:Bloody stools in a 5-day-old breastfed infant were possibly caused by concurrent maternal clindamycin 600 mg intravenously every 6 hours and gentamicin 80 mg intravenously every 8 hours. The infant's stools were reported to have normal flora and the stools became guaiac negative 24 hours after discontinuation of breastfeeding. On day 6 of age, the infant resumed breastfeeding after discontinuation of maternal antibiotics with no further difficulties. ◉ Effects on Lactation and Breastmilk:Relevant published information was not found as of the revision date.

来源:Drugs and Lactation Database (LactMed)

毒理性

• 在妊娠和哺乳期间的影响

◈ 克林霉素是什么？ 克林霉素是一种用于治疗或预防细菌感染的抗生素。它可以通过口服、皮肤外用或静脉注射（通过针头注入静脉）的方式使用。有时人们在发现自己怀孕后，会考虑改变用药方式，或者完全停止用药。然而，在做出任何改变之前，与您的医疗保健提供者交谈是非常重要的。您的医疗保健提供者可以与您讨论治疗您的疾病的好处以及怀孕期间未治疗疾病的风险。 ◈ 我正在服用克林霉素。它会让我更难怀孕吗？ 目前尚不清楚克林霉素是否会影响怀孕。 ◈ 服用克林霉素会增加流产的风险吗？ 任何怀孕都可能出现流产。一项涉及249名患有阴道细菌感染的女性的研究发现，克林霉素治疗减少了晚期流产和早产（提前分娩）的风险。 ◈ 服用克林霉素会增加出生缺陷的风险吗？ 每个怀孕都有3-5%的出生缺陷风险。这就是所谓的背景风险。使用克林霉素不太可能增加出生缺陷的风险。几项人类研究以及动物研究都没有显示出出生缺陷风险的增加。当克林霉素用于皮肤（外用）时，只有少量药物通过皮肤进入血液循环。这意味着怀孕期间接触的药物量非常小。由于关于阴道和口服克林霉素（与外用相比吸收更高）的现有信息没有发现出生缺陷风险的增加，因此使用外用克林霉素也不太可能增加出生缺陷的风险。 ◈ 孕期服用克林霉素会增加其他与怀孕相关问题的风险吗？ 几项研究没有发现孕期在第二或第三季度使用克林霉素会增加怀孕并发症的风险。 ◈ 孕期服用克林霉素会影响孩子的未来行为或学习吗？ 尚未进行研究以查看克林霉素是否会导致孩子的行为或学习问题。 ◈ 服用克林霉素时哺乳： 当女性通过口服或静脉注射（IV）方式接受克林霉素时，克林霉素会以少量进入母乳。在这种情况下，克林霉素可能会导致哺乳儿出现一些胃肠道（GI）副作用（例如恶心、腹泻、胃痛、呕吐、尿布疹、鹅口疮，或罕见的情况下血便）。皮肤外用（涂抹在皮肤上）的吸收量最小，不太可能以足以在您的宝宝中引起副作用的量进入母乳。如果您注意到您的孩子出现任何症状，请联系他们的医疗保健提供者。确保与您的医疗保健提供者讨论所有关于哺乳的问题。 ◈ 如果男性服用克林霉素，会影响生育能力（使伴侣怀孕的能力）或增加出生缺陷的风险吗？ 尚未进行研究以查看克林霉素是否会影响男性生育能力或增加出生缺陷的风险。一般来说，父亲或精子捐赠者的接触不太可能增加怀孕的风险。更多信息，请参阅MotherToBaby关于父亲接触的小册子，网址为https://mothertobaby.org/fact-sheets/paternal-exposures-pregnancy/。

◈ What is clindamycin? Clindamycin is an antibiotic used to treat or prevent bacterial infections. It can be taken by mouth (oral), used on the skin (topical), or given by IV (intravenous or by needle into a vein).Sometimes when people find out they are pregnant, they think about changing how they take their medication, or stopping their medication altogether. However, it is important to talk with your healthcare providers before making any changes to how you take this medication. Your healthcare providers can talk with you about the benefits of treating your condition and the risks of untreated illness during pregnancy. ◈ I take clindamycin. Can it make it harder for me to get pregnant? It is not known if clindamycin can make it harder to get pregnant. ◈ Does taking clindamycin increase the chance for miscarriage? Miscarriage can occur in any pregnancy. One study involving 249 women who had a vaginal bacterial infection found that clindamycin treatment reduced the chances of late miscarriage and preterm (early) births. ◈ Does taking clindamycin increase the chance of birth defects? Every pregnancy starts out with a 3-5% chance of having a birth defect. This is called the background risk.It is unlikely that using clindamycin increases the chance of birth defects. Several human studies as well as animal studies have not shown an increased chance of birth defects.When clindamycin is used on the skin (topical use), only small amounts pass through skin and get into the bloodstream. This means a pregnancy would be exposed to only a very small amount of the medicine. Since available information about vaginal and oral clindamycin (both higher absorptions compared to topical use) does not find an increased chance of birth defects, it is also unlikely that using topical clindamycin increases the chance of birth defects. ◈ Does taking clindamycin in pregnancy increase the chance of other pregnancy related problems? Several studies have not found an increased chance of pregnancy complications from clindamycin use in the second or third trimester. ◈ Does taking clindamycin in pregnancy affect future behavior or learning for the child? Studies have not been done to see if clindamycin can cause behavior or learning issues for the child. ◈ Breastfeeding while taking clindamycin: Clindamycin gets into breastmilk in small amounts when women are given clindamycin orally (by mouth) or intravenously (IV). In those situations, clindamycin might cause some gastrointestinal (GI) effects in a breastfeeding (e.g. nausea, diarrhea, stomach pain, vomiting, diaper rash, thrush, or rarely bloody stools). Topical application (to the skin) has minimal absorption into your circulation and are unlikely to end up in breast milk in amounts that might cause side effects in your baby. If you notice any symptoms in your child, contact their healthcare provider. Be sure to talk to your healthcare provider about all of your breastfeeding questions. ◈ If a male takes clindamycin, could it affect fertility (ability to get partner pregnant) or increase the chance of birth defects? Studies have not been done to see if clindamycin could affect male fertility or increase the chance of birth defects. In general, exposures that fathers or sperm donors have are unlikely to increase the risks to a pregnancy. For more information, please see the MotherToBaby fact sheet Paternal Exposures at https://mothertobaby.org/fact-sheets/paternal-exposures-pregnancy/.

来源:Mother To Baby Fact Sheets

毒理性

• 相互作用

抗生素诱导的小鼠膈神经-半膈肌准备的可逆性麻痹通过钙和通过新斯的明。

Reversibility of antibiotic-induced paralysis of mouse phrenic nerve-hemidiaphragm preparation by calcium and by neostigmine.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

同时使用含有高岭土或凹凸棒土的止泻药与口服克林霉素可能会显著延迟口服克林霉素的吸收；应避免同时使用，或建议患者在口服林可霉素前不少于2小时或后3至4小时服用吸附性止泻药。

Concurrent use of kaolin- or attapulgite-containing antidiarrheals with oral clindamycin may significantly delay the absorption of oral clindamycin; concurrent use should be avoided or patients should be advised to take adsorbent antidiarrheals not less than 2 hours before or 3 to 4 hours after oral lincomycins.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

克林霉素口服给药后几乎完全吸收。在摄入150毫克后，1小时内达到2至3微克/毫升的血浆峰浓度。胃中有食物存在并不减少吸收。这种抗生素的半衰期约为2.9小时，因此如果每6小时给药一次，可以预期会有适度的药物积累。

Clindamycin is nearly completely absorbed following oral admin. Peak plasma concn of 2 to 3 ug/mL are attained within 1 hr after the ingestion of 150 mg. The presence of food in stomach does not reduce absorption. The half-life of the antibiotic is about 2.9 hr, and the modest accumulation of drug is thus expected if it is given at 6-hr intervals.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

克林霉素广泛分布于许多液体和组织中，包括骨骼。即使在脑膜发炎时，也不会在脑脊液中达到显著浓度。治疗脑部弓形虫病所需的浓度是可以达到的。该药物容易穿过胎盘屏障。90%或更多的克林霉素与血浆蛋白结合。克林霉素在多形核白细胞、肺泡巨噬细胞和脓肿中积聚。

Clindamycin is widely distributed in many fluids and tissues, including bone. Significant concn are not attained in cerebrospinal fluid, even when the meninges are inflamed. Concn sufficient to treat cerebral toxoplasmosis are achievable .. The drug readily crosses the placental barrier. 90% or more of clindamycin is bound to plasma proteins. Clindamycin accumulates in polymorphonuclear leukocytes, alveolar macrophages, and in abscesses.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

半衰期在肾功能明显受损的患者中只是略微延长...

Half-life ... is lengthened only slightly in patients with markedly impaired renal function ...

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

克林霉素可分布到许多身体组织和体液中，包括唾液、腹水、胸水、滑液、骨骼和胆汁。然而，即使在存在炎症的脑脊液情况下，也只有少量药物能够扩散到脑脊液中。据报道，克林霉素在滑液和骨骼中的浓度是同时期血清浓度的60-80%；渗透程度似乎并不受关节炎症的影响。克林霉素容易穿过胎盘，脐带血中的药物浓度据报道是同时期母体血液浓度的46%。克林霉素也可分布到乳汁中。

Clindamycin is distributed into many body tissues and fluids including saliva, ascites fluid, pleural fluid, synovial fluid, bone, and bile. However, even in the presence of inflamed meninges, only small amounts of the drug diffuse into CSF. The concentration of clindamycin in synovial fluid and bone is reported to be 60-80% of concurrent serum concentrations of the drug; the degree of penetration does not appear to be affected by joint inflammation. Clindamycin readily crosses the placenta, and cord blood concentrations of the drug have been reported to be 46% of concurrent maternal blood concentrations. Clindamycin is distributed into milk.

来源:Hazardous Substances Data Bank (HSDB)

文献信息

• Small molecules active against gram-negative bacteria
  申请人：The Board of Trustees of the University of Illinois

  公开号：US10995097B2

  公开（公告）日：2021-05-04

  Disclosed are compounds that accumulate in Gram-negative bacteria. Also disclosed are method of antimicrobial treatment using the compounds.

  公开了可在革兰氏阴性细菌中蓄积的化合物。还公开了使用这些化合物进行抗菌治疗的方法。
• DRUG DELIVERY POLYMER WITH HYDROCHLORIDE SALT OF CLINDAMYCIN
  申请人：HALLIDAY Janet Anne

  公开号：US20080160065A1

  公开（公告）日：2008-07-03

  One embodiment provides an insert, which includes a non-degradable hydrogel matrix and clindamycin hydrochloride in contact with the matrix, wherein the insert is suitable for mammalian intravaginal, buccal, or intrarectal use. Methods of using and making the insert are also provided.
• SMALL MOLECULES ACTIVE AGAINST GRAM-NEGATIVE BACTERIA
  申请人：The Board of Trustees of the University of Illinois

  公开号：US20190135821A1

  公开（公告）日：2019-05-09

  Disclosed are compounds that accumulate in Gram-negative bacteria. Also disclosed are method of antimicrobial treatment using the compounds.
• US8007996B2
  申请人：——

  公开号：US8007996B2

  公开（公告）日：2011-08-30