(1S,2R,18R,19R,22S,25R,28R,40R)-48-{[(2S,3R,4S,5S,6R)-3-{[(2S,4S,6S)-4-amino-5-hydroxy-4,6-dimethyltetrahydro-2H-pyran-2-yl]oxy}-4,5-dihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl]oxy}-22-(2-amino-2-oxoethyl)-5,15-dichloro-2,18,32,35,37-pentahydroxy- - CAS号 1404-90-6

物化性质

熔点：

>274°C (dec.)
密度：

1.2882 (rough estimate)
溶解度：

二甲基亚砜（微溶）
稳定性/保质期：

When reconstituted with sterile water for injection, vancomycin hydrochloride injection is stable for 2 weeks at room temperature; the manufacturers state that reconstituted injections may be stored for 96 hours at 2 - 8 °C without substantial loss of potency. When reconstituted as directed in 0.9% sodium chloride injection or 5% dextrose injection, solutions prepared from ADD-Vantage vials of the drug are stable for 24 hours at room temperature. Vancomycin solutions containing 5 mg/mL in 0.9% sodium chloride injection or 5% dextrose injection are reportedly stable for at least 17 days when stored at 24 °C in glass or PVC containers and for at least 63 days when stored at 5 °C or -10 °C in glass containers. Following reconstitution with sterile water for injection as directed, vancomycin solutions that have been further diluted to a concentration of 5 mg/mL in 5 - 30% dextrose injection are stable when stored in plastic syringes for 24 hours at 4 eg C and then subsequently for 2 hours at room temperature.
分解：

When heated to decomposition, it emits toxic fumes of /nitric oxide/ and /chlorine/.
解离常数：

pka1 = 2.6; pKa2 = 7.2; pKa3 = 8.6; pKa4 = 9.6; pKa5 = 10.5; pKa6 = 11.7

计算性质

辛醇/水分配系数(LogP)：

-2.6
重原子数：

101
可旋转键数：

13
环数：

12.0
sp3杂化的碳原子比例：

0.42
拓扑面积：

531
氢给体数：

19
氢受体数：

26

ADMET

毒理性

肝毒性

静脉注射万古霉素与1%至5%的患者中血清转氨酶水平的轻微、短暂和无症状升高有关，但与此相比，类似或略低的异常率通常与比较药物有关。在罕见的情况下，血清酶升高更为明显，并可能伴有轻度症状，尽管通常没有黄疸。近年来，万古霉素与过敏反应有关，包括史蒂文斯-约翰逊综合征、中毒性表皮坏死松解症和药物反应、嗜酸性粒细胞增多和全身症状（DRESS）的独特综合征。这些形式的过敏通常在开始静脉注射（iv）万古霉素治疗后的几天到3到4周内出现。发热和严重的皮肤皮疹通常主导临床表现，但系统性症状可以包括肾脏、呼吸或心脏衰竭，中性粒细胞减少，血小板减少和肝脏损伤。与万古霉素相关的DRESS综合征的病例通常伴有血清酶升高（案例1），但显著升高、症状和黄疸并不常见。万古霉素诱导的DRESS综合征的典型系统性特征是肾脏而非肝脏损伤，但过敏反应的特征通常比器官特异性损伤更为突出。然而，在罕见的情况下，肝脏损伤可能很严重（案例2），并可能导致肝衰竭和死亡。接受静脉注射万古霉素的患者通常有多种并存疾病，包括败血症，并接受多种抗生素，这使得将过敏反应和肝脏损伤归因于万古霉素变得困难。其他更知名的DRESS综合征的原因包括别嘌醇、磺胺类药物和芳香味抗惊厥药。这些DRESS综合征的其他原因更可能与临床上明显的甚至致命的肝脏损伤有关。万古霉素也与几种急性输注反应有关，尤其是过敏性休克和万古霉素潮红反应，以前被称为“红人综合征”。万古霉素潮红反应通常发生在首次输注万古霉素的前15到20分钟内，尤其是在快速输注和高剂量（1000毫克在不到60分钟内输注）时。这种反应的特点是潮红、红斑和通常发生在面部、颈部和上躯干的瘙痒，有时伴有胸痛和背痛以及不同程度的低血压。罕见地，潮红反应与口服万古霉素治疗有关，尤其是在患有活动性结肠炎和肾功能障碍的老年患者中。症状的原因可能是万古霉素或金黄色葡萄球菌毒素对肥大细胞的急性脱颗粒作用。这种反应的介质是组胺和其他活性胺或肥大细胞颗粒中的成分。万古霉素潮红反应的人血浆组胺水平通常升高，但血浆组胺水平的变化与症状的严重程度的相关性较差。然而，万古霉素潮红反应的症状可以通过预先使用抗组胺药预防或减轻。也许更好的方法是使用较慢的输注速率和较低的万古霉素剂量。肝脏损伤不是万古霉素潮红反应的特征，但在持续或严重低血压的病例中可能会继发出现。可能性评分：B（通常是临床上明显肝脏损伤的高度可能原因，通常与DRESS综合征有关）。

Intravenous vancomycin is associated with minor, transient and asymptomatic elevations in serum aminotransferase levels in 1% to 5% of patients, but similar or minimally lower rates of abnormalities are usually reported with comparative agents. In rare instances, the serum enzyme elevations are more marked and may be associated with mild symptoms, although usually without jaundice. In recent years, vancomycin has been linked to hypersensitivity reactions, including Stevens-Johnson syndrome, toxic epidermal necrolysis and the distinctive syndrome of drug reaction, eosinophilia and systemic symptoms (DRESS). These forms of hypersensitivity generally arise within a few days to 3 to 4 weeks after initiation of intravenous (iv) vancomycin therapy. Fever and severe skin rash generally dominate the clinical presentation, but systemic symptoms can include renal, respiratory or heart failure, neutropenia, thrombocytopenia, and liver injury. Cases of DRESS syndrome associated with vancomycin are often accompanied by serum enzyme elevations (Case 1), but marked elevations, symptoms and jaundice are uncommon. The usual systemic features of vancomycin induced DRESS syndrome are renal rather than liver injury but features of hypersensitivity are usually more prominent than organ-specific injury. Nevertheless, in rare instances the liver injury can be severe (Case 2) and result in hepatic failure and death. Patients who receive intravenous vancomycin often have multiple comorbidities including sepsis and receive multiple antibiotics which make the attribution of the hypersensitivity reactions and liver injury with vancomycin difficult. Other more well-known causes of DRESS syndrome include allopurinol, sulfonamides, and the aromatic anticonvulsants. These other causes of DRESS syndrome are more likely to be associated with clinically apparent and even fatal liver injury. Vancomycin is also associated with several forms of acute infusion reactions, most notably anaphylaxis and the vancomycin flushing reaction, previously known as “red man syndrome”. Vancomycin flushing reactions occur typically during the first 15 to 20 minutes of an initial infusion of vancomycin, most commonly when given rapidly and in relative high doses (1000 mg given over less than 60 minutes). The reaction is characterized by flushing, erythema, and itching usually of the face, neck and upper torso, sometimes accompanied by chest and back pain and variable degrees of hypotension. Rarely, flushing reactions have been associated with oral vancomycin therapy, particularly in elderly patients with active colitis and renal dysfunction. The cause of the symptoms is probably the acute degranulation of mast cells by the direct effect of vancomycin or S. Aureus toxins. The mediator of the reaction is histamine and other active amines or components in mast cell granules. Plasma histamine levels are usually elevated in persons with vancomycin flushing reactions, but the correlation of changes in plasma histamine levels and severity of symptoms is poor. Nevertheless, the symptoms of the vancomycin flushing reaction can be prevented or ameliorated by pretreatment with antihistamines. Perhaps a better approach is the use of slower infusion rates and lower doses of vancomycin. Liver injury is not a feature of vancomycin flushing reactions but can arise secondarily in cases with prolonged or severe hypotension. Likelihood score: B (highly likely cause of clinically apparent liver injury usually in association with DRESS syndrome).

来源:LiverTox

毒理性

肝毒性

在获得许可前的对照试验中，使用Dalbavancin、Oritavancin或Telavancin治疗期间，血清ALT升高是常见的，发生在多达25%的患者中。然而，血清转氨酶升高超过正常上限三倍的情况并不常见，接受Dalbavancin、Oritavancin或Telavancin治疗的患者中，这种情况的发生率为0.8%至6%。此外，这些肝脏测试异常的发生率与对照臂并没有太大差异。在糖肽类抗生素治疗期间ALT升高通常是短暂的、无症状的，严重程度仅为轻至中度，很少导致剂量调整或提前终止治疗。在这些药物的注册试验中没有报告出现黄疸的临床明显肝损伤。自从这些药物获得批准并更广泛使用以来，没有公开发表的报告将肝损伤归因于糖肽类抗生素，尽管有报道过敏反应，有时可能与轻至中度的肝损伤有关。尽管如此，这三种药物相对较新，使用并不广泛，且使用时间相对较短，没有与严重肝损伤案例相关联。

In prelicensure controlled trials, serum ALT elevations during therapy with dalbvancin, oritavancin or telavancin were common, occurring in up to 25% of patients. Serum aminotransferase elevations above three times the upper limit of normal, however, were uncommon, occurring in 0.8% to 6% of patients receiving dalbavancin, oritavancin or telavancin. Furthermore, these rates of liver test abnormalities were not very different from those in comparator arms. The ALT elevations during glycopeptide antibiotic therapy were in general transient, asymptomatic and only mild-to-moderate in severity, rarely leading to dose modifications or early discontinuations. There were no reports of clinically apparent liver injury with jaundice in the registration trials of these agents. Since their approval and more wide scale use, there have been no published reports of liver injury attributed to glycopeptide antibiotics, although hypersensitivity reactions have been reported which can sometimes be associated with a mild-to-moderate degree of liver injury. Regardless, these three agents are relatively new, have not been widely used and when used, are given for a relatively short period of time and none have been linked to serious cases of liver injury.

来源:LiverTox

毒理性

相互作用

万古霉素与麻醉剂的联合使用已与过敏样反应以及输注反应（例如，低血压、潮红、红斑、荨麻疹、瘙痒）的频率增加有关。在接受万古霉素和麻醉剂的同时治疗的儿科患者中，出现了红斑和类似组胺的潮红。如果在诱导麻醉前1小时给予万古霉素静脉输注，可能会最小化输注相关的不良反应的风险。

Concomitant use of vancomycin and anesthetic agents has been associated with anaphylactoid reactions and an increased frequency of infusion reactions (e.g., hypotension, flushing, erythema, urticaria, pruritus). Erythema and histamine-like flushing has occurred in pediatric patients receiving vancomycin and anesthetic agents concomitantly. The risk of infusion-related adverse effects may be minimized if vancomycin is given as a 1-hour IV infusion prior to induction of anesthesia.