(2S,4R)-N-[(1R)-2-chloro-1-[(2R,3R,4S,5R,6S)-3,4,5-trihydroxy-6-methylsulfanyloxan-2-yl]propyl]-1-methyl-4-propylpyrrolidine-2-carboxamide

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (2S,4R)-N-[(1R)-2-chloro-1-[(2R,3R,4S,5R,6S)-3,4,5-trihydroxy-6-methylsulfanyloxan-2-yl]propyl]-1-methyl-4-propylpyrrolidine-2-carboxamide
• 化学式: C₁₈H₃₃ClN₂O₅S
• 分子量: 425.0
• InChiKey: KDLRVYVGXIQJDK-NQQGAZBYSA-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：
  0.94
• 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的代谢物。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；其余的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%的克林霉素以原形在尿液中排泄，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而失活，这些代谢物通过尿液和胆汁排出体外。

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：通常是短暂性的血清转氨酶升高，通常在连续几天接受高剂量静脉注射后出现；以及急性特异质性肝损伤，这种损伤在开始治疗后的1到3周内发生，通常病情较轻且自限性。 高剂量的静脉注射克林霉素可能会导致血清ALT水平升高，升高范围在正常上限的2到10倍之间，这种情况通常在治疗开始后5到15天内出现，与静脉注射苯唑西林治疗时的情况相似（案例1）。如果出现症状、黄疸和碱性磷酸酶升高，通常也是轻微的（案例2），并且一旦停止克林霉素治疗或转为较低剂量或口服制剂，转氨酶水平会迅速降至正常范围（1到2周内）。 克林霉素治疗也与在开始口服或胃肠外治疗后的1到3周内发生的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，但往往不明显，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。肝损伤通常为轻到中度，停药后迅速好转。然而，也有致命的病例报告。 可能性评分：B（高度可能是明显临床肝损伤的原因）。

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

• 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，或者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)

毒理性

• 相互作用

体外实验有证据表明红霉素和克林霉素之间存在拮抗作用。

There is in vitro evidence of antagonism between erythromycin and clindamycin.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

克林霉素据报道在体外对抗氨基糖苷类抗生素的杀菌活性，一些临床医生建议不要同时使用这些药物。然而，体内拮抗作用尚未得到证实，克林霉素与氨基糖苷类药物联合使用时，并未出现明显的活性降低。

Clindamycin has been reported to antagonize the bactericidal activity of aminoglycosides in vitro, and some clinicians recommend that these drugs not be used concomitantly. However, in vivo antagonism has not been demonstrated, and clindamycin has been administered successfully in conjunction with an aminoglycoside with no apparent decrease in activity.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

克林霉素在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/毫升的峰值血浆浓度。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

克林霉素在许多液体和组织中广泛分布，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累。

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会略微延长...

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

克林霉素被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的情况下，也只有少量药物能扩散到脑脊液中。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%；穿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%。克林霉素也会分布到乳汁中。

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)