[(1S,4aR,11S,11aS,12aS)-3-carbamoyl-10-chloro-4,4a,6,7,11-pentahydroxy-2,5-dioxo-11,11a,12,12a-tetrahydro-1H-tetracen-1-yl]-dimethylazanium;chloride

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 四环素类
• 英文名称: [(1S,4aR,11S,11aS,12aS)-3-carbamoyl-10-chloro-4,4a,6,7,11-pentahydroxy-2,5-dioxo-11,11a,12,12a-tetrahydro-1H-tetracen-1-yl]-dimethylazanium;chloride
• 化学式: C21H22Cl2N2O8
• 分子量: 501.3
• InChiKey: OAPVUSSHCBRCOL-KBHRXELFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.53
• 重原子数：
  33
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  182
• 氢给体数：
  7
• 氢受体数：
  9

ADMET

毒理性

• 肝毒性

没有关于去甲氯四环素导致肝损伤的报道发表。然而，去甲氯四环素是一种四环素衍生物，可能会像其他口服四环素一样导致肝损伤。去甲氯四环素的产品标签中提到了肝炎和肝衰竭，但没有提供肝损伤的详细信息。最后，去甲氯四环素会导致肝硬化患者的肾功能恶化，不应用于治疗与慢性肝病相关的低钠血症。 可能性评分：E*（疑似但未证实的临床明显肝损伤原因）。 药物类别：抗感染药物，四环素类

No reports of liver injury due to demeclocycline have been published. However, demeclocycline is a tetracycline derivative and is likely to cause liver injury similar to other oral tetracyclines. Both hepatitis and liver failure are mentioned in the product label for demeclocycline, but details of the liver injury are not provided. Finally, demeclocycline causes worsening of kidney function in patients with cirrhosis and should not be used for hyponatremia associated with chronic liver disease. Likelihood score: E* (suspected but unproven cause of clinically apparent liver injury). Drug Class: Antiinfective Agents, Tetracyclines

来源:LiverTox

毒理性

• 相互作用

PRERENAL AZOTEMIA & DRUG TOXICITY MAY ARISE WHEN TETRACYCLINES ARE ADMIN TO PT WITH DECR RENAL FUNCTION. METHOXYFLURANE IS ASSOC WITH DOSE-RELATED IMPAIRMENT OF RENAL FUNCTION, SO POTENTIAL FOR TETRACYCLINE TOXICITY MAY BE INCR FOLLOWING...ANESTHESIA. ... ALL TETRACYCLINES EXCEPT DOXYCYCLINE MAY EXHIBIT SAME...TOXICITY. 当给肾功能减退的患者使用四环素类药物时，可能会出现肾前性氮质血症和药物毒性。甲氧氟烷与剂量相关的肾功能损害有关，因此在麻醉后，四环素类药物的毒性潜力可能会增加。除了多西环素外的所有四环素类药物可能表现出相同的毒性。

PRERENAL AZOTEMIA & DRUG TOXICITY MAY ARISE WHEN TETRACYCLINES ARE ADMIN TO PT WITH DECR RENAL FUNCTION. METHOXYFLURANE IS ASSOC WITH DOSE-RELATED IMPAIRMENT OF RENAL FUNCTION, SO POTENTIAL FOR TETRACYCLINE TOXICITY MAY BE INCR FOLLOWING...ANESTHESIA. ... ALL TETRACYCLINES EXCEPT DOXYCYCLINE MAY EXHIBIT SAME...TOXICITY.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

铝、钙或镁离子同时给药会显著降低四环素的吸收。... /地美罗辛/ 曾有报道称与含铝离子的铝以及含钙的乳制品（例如，白软干酪和牛奶）发生相互作用。

SIMULTANEOUS ADMIN OF ALUMINUM, CALCIUM, OR MAGNESIUM IONS SIGNIFICANTLY DECR GI ABSORPTION OF TETRACYCLINE. ... /DEMECLOCYLINE HAS/ BEEN REPORTED TO INTERACT WITH ALUMINUM IONS & DAIRY PRODUCTS CONTAINING CALCIUM (EG, COTTAGE CHEESE & MILK).

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

因为甲氨蝶呤会与血浆蛋白结合，它可以从结合位点被替换下来，并变得可供与二氢叶酸还原酶反应。据报道，能够替换甲氨蝶呤的化合物包括...四环素类。

BECAUSE METHOTREXATE BINDS TO PLASMA PROTEINS, IT CAN BE DISPLACED FROM ITS BINDING SITES & MADE AVAIL TO REACT WITH DIHYDROFOLATE REDUCTASE. THOSE COMPD THAT HAVE BEEN REPORTED TO DISPLACE METHOTREXATE INCL...TETRACYCLINES.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

四环素可能会拮抗青霉素的杀菌效果，但在临床上显著相互作用的情况只出现在需要快速杀菌效果的情况下（例如，肺炎球菌性脑膜炎）。...所有四环素类药物都可能会以类似方式相互作用...

TETRACYCLINE MAY ANTAGONIZE BACTERICIDAL EFFECT OF PENICILLIN, BUT CLINICALLY SIGNIFICANT INTERACTION OCCURS ONLY IN SITUATIONS WHERE RAPID BACTERICIDAL EFFECT IS NECESSARY (EG, PNEUMOCOCCAL MENINGITIS). ... ALL TETRACYCLINES MAY BE EXPECTED TO INTERACT IN SIMILAR MANNER...

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

四环素在妊娠期间和整个儿童期会沉积在骨骼中。

Tetracyclines are deposited in the skeleton during gestation & throughout childhood. /Tetracyclines/

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

四环素类药物在体内广泛分布，包括组织和分泌物，如尿液和前列腺。它们在肝脏、脾脏和骨髓的网状内皮细胞中积累，以及在骨骼、牙本质和未萌出牙齿的牙釉质中。/四环素类药物/

Tetracyclines distribute widely throughout the body & into tissues & secretions, including the urine & prostate. They accumlate in the reticuloendothelial cells of the liver, spleen, & bone marrow, & in bone, dentine, & the enamel of unerupted teeth. /Tetracyclines/

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

四环素类药物可以通过胎盘进入胎儿循环和羊水。在脐带血浆中四环素的浓度可达到母体循环中的60%，在羊水中则达到20%。这些药物在母乳中也有相对较高的浓度。/四环素类药物/

Tetracyclines cross the placenta & enter the fetal circulation & amniotic fluid. Concn of tetracycline in umbilical-cord plasma reach 60%, & in amniotic fluid 20%, of those in the circulation of the mother. Relatively high concns of these drugs also are found in breast milk. /Tetracyclines/

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

在大鼠口服去甲基氯四环素（游离碱和盐酸形式）后，来自每种形式的血浆水平基本相同。

AFTER ORAL ADMIN OF DEMETHYLCHLORTETRACYCLINE (FREE BASE & HCL SALT) TO RATS, PLASMA LEVELS FROM EACH WERE ESSENTIALLY IDENTICAL.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

新一代的四环素类药物是指那些在美国可用但未经批准用于兽医用途的四环素。这些包括地去氧氯四环素、甲氯四环素、多西环素和米诺环素。其中，多西环素和米诺环素似乎具有某些优势，使它们在兽医医学的某些情况下变得有用。它们的主要优势在于相对于其他四环素类药物，它们具有更大的脂溶性。这一特性可能是它们对某些微生物具有增强的抗菌效果、口服给药后吸收更高效以及在体内分布增强的原因。多西环素的主要排泄器官是小肠，药物通过肠粘膜扩散到肠腔中。这一独特特性使得这种药物在预先存在肾功能不全的情况下变得有用，并可能使这种药物在治疗肠道感染方面优于其他四环素类药物。在其他国家，多西环素用于治疗家禽的呼吸道和肠道疾病。由于药物残留的持久性，多西环素和米诺环素在食品生产动物中的使用可能受限。米诺环素在大剂量下，与链霉素联合使用，用于消除犬布鲁氏菌病的携带状态。多西环素和米诺环素相对于其他四环素类药物，在分布到身体如眼睛、大脑、脑脊液和前列腺等区域方面的优势表明，它们在治疗这些区域的四环素敏感感染的有效性试验是有指征的。对于家畜，尚未进行旨在确定最佳剂量方案的药代动力学研究。这些确定是必要评估新一代四环素类药物在兽医医学中的有效性的。

The newer tetracyclines are defined as those tetracyclines available in the United States but not approved for veterinary use. These include demeclocycline, methacycline, doxycycline, & minocycline. Of these, doxycycline & minocycline appear to offer advantages that would render them useful in certain situations in veterinary medicine. Their major advantage lies in their greater lipid solubility relative to other tetracyclines. This characteristic probably accounts for their enhanced antimicrobial effectiveness for some organisms, more efficient absorption after oral admin, & enhanced distribution in the body. The principal excretory organ for doxycycline is the intestine, where the drug diffuses through the intestinal mucosa into the intestinal tract. This unique characteristic makes this drug useful in cases of preexisting renal dysfunction & may render this drug superior to other tetracyclines in the treatment of intestinal infections. Doxycycline is used in other countries for respiratory tract & intestinal tract diseases of poultry. The usefulness of doxycycline & minocycline in food-producing animals may be limited because of persistent drug residues. Minocycline has, in large doses, been used with streptomycin in the elimination of the carrier state of canine brucellosis. The superiority of doxycycline & minocycline, relative to other tetracyclines, in their distribution to areas of the body such as the eye, brain, cerebrospinal fluid, & prostate gland suggests that trials of their efficacy in tetracycline-sensitive infections of these areas are indicated. Pharmacokinetic studies designed to determine optimal dosage schedules have not been made for domestic animals. These determinations are necessary to evaluate most effectively the usefulness of the newer tetracyclines in veterinary medicine.

来源:Hazardous Substances Data Bank (HSDB)