N-(1,2,3,10-四甲氧基-9-氧代-5,6,7,9-四氢苯并[a]庚搭烯-7-基)乙酰胺 | 54192-66-4

• 分子结构分类: 有机化合物 - 碳氢化合物衍生物 - 环庚三烯酮
• 中文名称: N-(1,2,3,10-四甲氧基-9-氧代-5,6,7,9-四氢苯并[a]庚搭烯-7-基)乙酰胺
• 英文名称: N-(5,6,7,9-tetrahydro-1,2,3,10-tetramethoxy-9-oxobenzo[a]heptalen-7-yl) acetamide
• 英文别名: (7RS)-colchicine；Colchicine；7-acetylamino-1,2,3,10-tetramethoxy-6,7-dihydro-5H-benzo[a]heptalen-9-one；(+/-)-colchicine；(+/-)-7-Acetylamino-1,2,3,10-tetramethoxy-6,7-dihydro-5H-benzo[a]heptalen-9-on；(+/-)-Colchicin；N-(1,2,3,10-Tetramethoxy-9-oxo-5,6,7,9-tetrahydrobenzo[a]heptalen-7-yl)acetamide；N-(1,2,3,10-tetramethoxy-9-oxo-6,7-dihydro-5H-benzo[a]heptalen-7-yl)acetamide
• CAS: 54192-66-4
• 化学式: C₂₂H₂₅NO₆
• mdl: MFCD00001179
• 分子量: 399.444
• InChiKey: IAKHMKGGTNLKSZ-UHFFFAOYSA-N

物化性质

• 熔点：
  280-282 °C
• 沸点：
  726.0±60.0 °C(Predicted)
• 密度：
  1.25±0.1 g/cm3(Predicted)
• 物理描述：
  Colchicine appears as odorless or nearly odorless pale yellow needles or powder that darkens on exposure to light. Used to treat gouty arthritis, pseudogout, sarcoidal arthritis and calcific tendinitis. (EPA, 1998)
• 颜色/状态：
  Pale yellow scales or powder; pale yellow needles when crystallized from ethyl acetate
• 气味：
  Odorless or nearly so
• 溶解度：
  At 25 °C, 4.5 g/100 g water
• 蒸汽压力：
  3.2X10-11 mm Hg at 25 °C (est)
• 稳定性/保质期：

  Colchicine able to withstand drying, storage, and boiling.

• 旋光度：
  Specific optical rotation: -429 at 17 °C/D (water, 1.72%); -121 deg at 17 °C/d (concentration by volume = 0.9 g in 100 ml chloroform); max absorption (95% ethanol): 350.5 nm (log epsilon = 4.22), 243 nm (log epsilon = 4.47)
• 分解：
  When heated to decomposition, colchicine emits toxic fumes of carbon monoxide, carbon dioxide, and nitrogen oxides.
• 解离常数：
  pKa = 1.85

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  29
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.363
• 拓扑面积：
  83.1
• 氢给体数：
  1
• 氢受体数：
  6

ADMET

代谢

秋水仙碱在肝脏中被发现代谢，并去甲基化为主要代谢物，包括2-O-去甲基秋水仙碱和3-O-去甲基秋水仙碱，以及一个次要代谢物，10-O-去甲基秋水仙碱（秋水仙碱）。根据体外研究，CYP3A4将秋水仙碱代谢为2-和3-去甲基秋水仙碱。

Colchicine is found to be metabolized in the liver and demethylated to major metabolites, which include 2-O-demethylcolchicine and 3-O-demethylcolchicine, and one minor metabolite, 10-O-demethylcolchicine (colchiceine). According to in vitro studies, CYP3A4 metabolizes colchicine to 2- and 3-demethylcolchicine.

来源:DrugBank

代谢

秋水仙碱经历部分肝脏代谢。秋水仙碱在肝脏中部分脱乙酰化。大量的秋水仙碱及其代谢物经历肠肝循环。这可以解释在摄入后5到6小时观察到的第二个血浆峰浓度出现的原因。

Colchicine undergoes some hepatic metabolism. Colchicine is partially deacetylated in the liver. Large amounts of colchicine and of its metabolites undergo enterohepatic circulation. This may explain the occurrence of a second plasma peak concentration observed 5 to 6 hours after ingestion.

来源:Hazardous Substances Data Bank (HSDB)

代谢

三种新的秋水仙碱结合代谢物在大鼠胆汁中被鉴定出来，这是通过增强的在线液相色谱-精确放射性同位素计数技术实现的。已知的2-和3-去甲基秋水仙碱（DMCs）除了之前描述的O-葡萄糖苷酸化之外，还发生了O-硫酸盐结合。2-DMC主要发生O-葡萄糖苷酸化，而3-DMC主要产生O-硫酸盐结合物，这表明了第二阶段结合的区域选择性。此外，M1被鉴定为一种新的谷胱甘肽结合物，并提出了其形成的可能生物转化途径。已知的2-DMC（M6）、3-DMC（M7）、2-DMC葡萄糖苷酸（M4）和新的3-DMC硫酸盐（M3）被确认为主要代谢物。

Three novel conjugation metabolites of colchicine were identified in rat bile facilitated by enhanced on-line liquid chromatography-accurate radioisotope counting. The known 2- and 3-demethylcolchicines (DMCs) underwent O-sulfate conjugation in addition to the previously described O-glucuronidation. 2-DMC was preferably O-glucuronidated, whereas 3-DMC predominantly yielded O-sulfation conjugates, indicating phase II conjugation regiopreferences. Moreover, M1 was identified as a novel glutathione conjugate and a possible biotransformation pathway for its formation was proposed. The known 2-DMC (M6), 3-DMC (M7), 2-DMC glucuronide (M4), and novel 3-DMC sulfate (M3) were confirmed as the major metabolites. ...

来源:Hazardous Substances Data Bank (HSDB)

代谢

可能是肝脏的。尽管尚未在人体内识别秋水仙碱代谢物，但已通过体外实验证明，哺乳动物肝脏微粒体可代谢秋水仙碱。 消除途径：在健康志愿者（n=12）中，40-65%的口服给药秋水仙碱（1毫克）以原形在尿液中回收。 肠肝循环和胆汁排泄也被假设在秋水仙碱的消除中发挥作用。 半衰期：在健康受试者中，消除半衰期大约为1小时，尽管一项延长采样时间的研究报告称，平均终末消除半衰期值大约为9至10.5小时。其他研究报道，酒精性肝硬化患者的半衰期值大约为2小时，家族性地中海热患者的半衰期值大约为2.5小时。

Probably hepatic. Although colchicine metabolites have not been identified in humans, metabolism by mammalian hepatic microsomes has been demonstrated in vitro. Route of Elimination: In healthy volunteers (n=12) 40 - 65% of 1 mg orally administered colchicine was recovered unchanged in urine. Enterohepatic recirculation and biliary excretion are also postulated to play a role in colchicine elimination. Half Life: Elimination half-life is approximately 1 hour in healthy subjects, although a study with an extended sampling time reported mean terminal elimination half-life values of approximately 9 to 10.5 hours. Other studies have reported half-life values of approximately 2 hours in patients with alcoholic cirrhosis and approximately 2.5 hours in patients with familial Mediterranean fever.

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 毒性总结

识别：秋水仙碱是一种抗痛风制剂。秋水仙碱可以制成片剂，在一些国家也可以制成注射溶液。秋水仙碱是秋水仙（秋季藏红花，草地藏红花）的一种生物碱。秋水仙也存在于火焰百合中。秋水仙碱是一种淡黄色的无味粉末或鳞片。遇光变暗。秋水仙碱用于治疗急性痛风发作，以减轻疼痛和炎症。它可能长期使用以预防或减少发作频率。秋水仙碱长期使用可预防发热和复发性多浆膜炎。秋水仙碱有效预防这种状况下的淀粉样变。秋水仙碱已被证明在治疗关节、皮肤和粘膜症状方面有效。秋水仙碱已用于治疗硬皮病和结节病。人类暴露：主要风险和靶器官：秋水仙碱产生多器官毒性。主要毒性效应与秋水仙碱对细胞分裂的影响有关，包括腹泻、骨髓抑制、脱发。其他急性效应包括低血容量、休克和凝血障碍，可能导致死亡。临床效应总结：毒性表现出现在摄入或注射后2至12小时的延迟。症状学在三个阶段发展：第一阶段（第1至3天）胃肠循环阶段：严重的胃肠刺激：恶心、呕吐、腹痛、严重腹泻。脱水、低血容量、休克。心源性休克可能发生，可能在头72小时内导致死亡。呼吸不足、急性呼吸窘迫综合征。第二阶段（第3至10天）骨髓发育不良阶段：骨髓发育不良伴粒细胞缺乏。弥漫性出血的凝血障碍。横纹肌溶解、多发性神经病、肌病、急性肾衰竭和感染。第三阶段：（10天后）恢复期：脱发。进入途径：口服：口服吸收是中毒的最常见原因。注射：注射后中毒很少见，然而，毒性剂量似乎低于口服毒性剂量。一名70岁男子在5天内接受10毫克静脉注射秋水仙碱后出现致命的骨髓发育不良。将秋水仙碱注入阴茎尿道治疗尖锐湿疣后出现多系统反应。吸收途径：口服：从胃肠道快速吸收。摄入后0.5至2小时达到血浆峰浓度。吸收半衰期为15分钟。吸收可能受到pH值、胃内容物、肠道活动的影响。秋水仙碱不是完全吸收。有一个重要的肝脏首过效应。秋水仙碱分布在一个大于身体的体积中。在严重的肾脏或肝脏疾病中，分布体积较小。秋水仙碱在肾脏、肝脏、脾脏、胃肠壁和白细胞中积聚，在心脏、大脑、骨骼肌中显然被排除。秋水仙碱穿过胎盘，也已在母体乳汁中发现。生物半衰期：注射：单次2毫克静脉注射后，平均血浆半衰期为20分钟。在严重肾脏疾病（40分钟）时，血浆半衰期增加，在严重肝脏疾病（9分钟）时减少。口服：口服给药后，血浆浓度在0.5至2小时内达到峰值，然后在2小时内迅速下降。血浆半衰期为60分钟。秋水仙碱可能在组织中停留长达10天。代谢：秋水仙碱在肝脏发生一些代谢。秋水仙碱在肝脏部分脱乙酰化。大量的秋水仙碱及其代谢物发生肠肝循环。这可以解释在中毒后5至6小时观察到的第二个血浆峰浓度。消除途径：秋水仙碱以原形（10至20%）或代谢物形式排泄。口服：尿排泄量占给药量的16至47%。50至70%的秋水仙碱以原形排出，30至50%以代谢物排出。在头24小时内，20%的给药量在尿液中排出，27.5%在头48小时内排出。秋水仙碱在中毒后7至10天内在尿液中检测到。尿排泄在肝功能受损的患者中增加。胆汁：10至25%的秋水仙碱在胆汁中排泄。粪便：大量药物在粪便中排泄。母乳：秋水仙碱可能在母乳中排出。静脉注射：粪便：静脉注射后，10至56%在头48小时内通过粪便排出。母乳：秋水仙碱可能在母乳中排出。作用机制：秋水仙碱与微管蛋白结合，这阻止了其聚合成微管。这种结合是可逆的，秋水仙碱-微管蛋白复合物的半衰期是36小时。秋水仙碱损害微管的各种细胞功能：有丝分裂过程中染色体对的分离（因为秋水仙碱在有丝分裂中期阻断有丝分裂）、阿米巴运动、吞噬作用。有丝分裂阻断导致腹泻、骨髓抑制和脱发。秋水仙碱可能对肌肉、外周神经系统、肝脏有直接毒性作用。然而，细胞功能抑制并不解释严重过量时观察到的所有器官衰竭。药效学：痛风炎症是由组织

IDENTIFICATION: Colchicine is an antigout preparations. Colchicine is available as tablets and, in some countries, as injectable solutions. Colchicine is an alkaloid of Colchicum autumnale (autumn crocus, meadow saffron). Colchicum is also present in Gloriosa superba. Colchicine is a pale yellow odorless powder or scales. It darkens on exposure to light. Colchicine is used for acute gout attacks to reduce pain and inflammation. It may be used on long-term basis to prevent or reduce the frequency of attacks. Colchicine is used on long-term basis to prevent fever and recurrent polyserositis. Colchicine is effective in preventing the amyloidosis in this condition. Colchicine has been showed to be effective in the treatment of articular, cutaneous and mucosal symptoms. Colchicine has been used in the treatment of scleroderma and sarcoidosis. HUMAN EXPOSURE: Main risks and target organs: Colchicine exerts a multiorgan toxicity. The main toxic effects are related to the effects of colchicine on cellular division and account for diarrhea, bone marrow depression, alopecia. Other acute effects are hypovolemia, shock, and coagulation disturbances, which may lead to death. Summary of clinical effects: Toxic manifestations appear after a delay of 2 to 12 hours following ingestion or parenteral administration. Symptomatology progresses in three stages: Stage I (Day 1 to 3) gastrointestinal and circulatory phase: Severe gastrointestinal irritation: Nausea, vomiting, abdominal cramps, severe diarrhea. Dehydration, hypovolemia, shock. Cardiogenic shock may occur and may result in death within the first 72 hours. Hypoventilation, acute respiratory distress syndrome. Stage II (Day 3 to 10) bone marrow aplasia phase: Bone marrow aplasia with agranulocytosis. Coagulation disorders with diffuse hemorrhages. Rhabdomyolysis, polyneuritis, myopathy, acute renal failure and infections. Stage III: (After 10 day) recovery phase: Alopecia. Routes of entry: Oral: Oral absorption is the most frequent cause of intoxication. Parenteral: Intoxications after parenteral administration are rare, however, the toxic dose appears to be lower than the oral toxic dose. A fatal bone marrow aplasia in a 70 year-old man after 10 mg intravenous colchicine over 5 days. Intoxication with multisystemic reactions after instillation of colchicine into the penile urethra for treatment of condyloma acuminata. Absorption by route of exposure: Oral: Rapidly absorbed from the gastro-intestinal tract. Peak plasma concentration is reached 0.5 to 2 hours after ingestion. Half time of absorption is 15 minutes. Absorption may be modified by pH, gastric contents, intestinal motility. Colchicine is not totally absorbed. There is an important hepatic first pass effect. Colchicine distributes in a space larger than that of the body. In severe renal or liver diseases the volume of distribution is smaller. Colchicine accumulates in kidney, liver, spleen, gastro-intestinal wall and leucocytes and is apparently excluded in heart, brain, skeletal muscle. Colchicine crosses the placenta and has also been found in maternal milk. Biological half-life by route of exposure: Parenteral: After a single 2 mg intravenous dose the average plasma half-life is 20 minutes. Plasma half-life is increased in severe renal disease (40 min) and decreased in severe hepatic disease (9 min). Oral: After oral administration plasma concentrations reach a peak within 0.5 to 2 hours and afterwards decrease rapidly within 2 hours. The plasma half-life is 60 minutes. Colchicine may remain in tissues for as long as 10 days. Metabolism: Colchicine undergoes some hepatic metabolism. Colchicine is partially deacetylated in the liver. Large amounts of colchicine and of its metabolites undergo enterohepatic circulation. This may explain the occurrence of a second plasma peak concentration observed 5 to 6 hours after ingestion. Elimination by route of exposure: Colchicine is excreted unchanged (10 to 20 percent) or as metabolites. Oral: Urinary excretion amount to 16 to 47% of an administered dose. 50 to 70% of colchicine is excreted unchanged and 30 to 50% as metabolites. 20% of the dose administered is excreted in urine in the first 24 hours and 27.5% in the first 48 hours. Colchicine is detected in urine up to 7 to 10 days after ingestion. Urinary excretion is increased in patients with impaired hepatic function. Bile: 10 to 25% of colchicine is excreted in the bile. Feces: Large amounts of the drug are excreted in the feces. Breast Milk: Colchicine may be eliminated in breast milk. Intravenous: Feces: After intravenous administration 10 to 56% is excreted in the feces within the first 48 hours. Breast Milk: Colchicine may be eliminated in breast milk. Mode of action: Colchicine binds to tubulin and this prevents its polymerization into microtubules. The binding is reversible and the half-life of the colchicine-tubulin complex is 36 hours. Colchicine impairs the different cellular functions of the microtubule: separation of chromosome pairs during mitosis (because colchicine arrests mitosis in metaphase), ameboid movements, phagocytosis. Mitosis blockade accounts for diarrhoea, bone marrow depression and alopecia. Colchicine may have a direct toxic effect on muscle, peripheral nervous system and liver. Inhibition of cellular function does not, however, account for all the organ failures seen in severe overdose. Pharmacodynamics: Gout inflammation is initiated by urate crystals within tissues. The crystals are ingested by neutrophils but this leads to the release of enzymes and the destruction of the cells. Chemotactic factors are released and attract more neutrophils. Colchicine may act by preventing phagocytosis, the release of chemotactic factors and the response of neutrophils. Colchicine has other properties such as antipyretic effects, respiratory depression, vasoconstriction and hypertension. Adults: Oral: The severity and the mortality rate of the poisoning is directly related to the dose ingested. Intravenous: A fatal bone marrow aplasia in a 70-year-old patient is reported. The enhanced toxicity of intravenous colchicine is probably due to the higher bioavailability of colchicine after parenteral administration. Teratogenicity: Colchicine is contraindicated in pregnancy as Down's syndrome and spontaneous abortion have been reported. Colchicine should be discontinued three months prior to conception. Interactions: A case of acute cyclosporin nephrotoxicity induced by colchicine administration has been reported. Colchicine may interfere with cyclosporin pharmacokinetics by increasing cyclosporin plasma levels either by enhancing cyclosporin absorption or by reducing its hepatic metabolism. Main adverse effects: Gastrointestinal symptoms are a common complication of chronic colchicine therapy. Fatal outcomes have been reported after intravenous colchicine therapy. Gastrointestinal: vomiting, diarrhoea, abdominal discomfort, paralytic ileus, malabsorption syndrome with steatorrhea. Hematological: Bone marrow depression with agranulocytosis, acute myelomonocytic leukaemia, multiple myeloma, thrombocytopenia. Neurological: Peripheral neuritis, myopathy and rhabdomyolysis. Dermatological: Allergic reactions are rare urticaria; oedema may be seen. Alopecia has been reported after chronic treatment. Reproductive system: A reversible, complete azoospermia has been reported. Metabolic: Colchicine is capable of producing a reversible impairment of vitamin B12 absorption. Porphyria cutanea tarda has been reported. Others: Hyperglycemia has been reported in a 58-year-old woman who ingested colchicine and developed transient diabetes mellitus has been reported. Hyperlipemia: A transient hyperlipemia has been reported. Hyperuricemia: A transient hyperuricemia has also been noted. Hyperthermia-fever: Occurrence of fever may be relate to an infectious complication, especially during the stage of aplasia. Special risks: Pregnancy: Two cases of Down's syndrome babies have been reported. The obstetric histories of 36 women with familial Mediterranean fever on long-term colchicine treatment between 3 and 12 years have been reported. Seven of 28 pregnancies ended in miscarriage. Thirteen women had periods of infertility. All 16 infants born to mothers who had taken colchicine during pregnancy were healthy. The authors do not advise discontinuation of colchicine before planned pregnancy but recommend amniocentesis for karyotyping and reassurance. Breast-feeding: As colchicine is eliminated in the breast milk breast-feeding should be avoided.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 毒性总结

秋水仙碱通过结合并干扰微管亚单位微管蛋白的聚合，从而抑制包括白细胞在内的多种细胞的微管组装。尽管一些研究发现这种行为可能并不显著有助于秋水仙碱的抗痛风作用，但最近的一项体外研究表明，它至少在某种程度上参与了这一过程。

Colchicine inhibits microtubule assembly in various cells, including leukocytes, probably by binding to and interfering with polymerization of the microtubule subunit tubulin. Although some studies have found that this action probably does not contribute significantly to colchicine's antigout action, a recent in vitro study has shown that it may be at least partially involved.

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 致癌物分类

对人类无致癌性（未列入国际癌症研究机构IARC清单）。

No indication of carcinogenicity to humans (not listed by IARC).

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 在妊娠和哺乳期间的影响

◉ 母乳喂养期间的使用总结：长期预防性给予母亲的秋水仙碱剂量高达每日1.5毫克，产生的乳汁中的水平导致婴儿接受的母亲体重调整剂量的不到10%。乳汁中最高水平出现在给药后2到4小时，因此在这段时间避免哺乳可以最小化婴儿的剂量，尽管一些临床医生简单地建议在哺乳后服用药物。在病例系列和病例对照研究中，没有报道哺乳婴儿出现不良影响，并且许多专家和专业指南认为在治疗家族性地中海热或风湿病状况的哺乳期妇女中，秋水仙碱是安全的。 ◉ 对哺乳婴儿的影响：在4名母亲每天预防性服用1到1.5毫克秋水仙碱用于治疗家族性地中海热的婴儿中，至少10个月的临床随访中没有发现明显的影响。作者还报告说，他们回想起另外6名妇女在秋水仙碱治疗期间（剂量未说明）至少哺乳了3个月的婴儿，至少2年的随访没有发现临床或发育问题。 一名婴儿在母亲每天两次服用秋水仙碱0.6毫克的情况下哺乳了6个月。没有发现明显的不良影响。 在一项关于母亲在怀孕期间服用秋水仙碱的研究中，181名母亲中有111名报告了哺乳（程度未说明）他们的婴儿。据报道，没有婴儿出现秋水仙碱相关的不良影响。 在一项病例对照研究中，将37名在哺乳期间服用秋水仙碱的妇女及其38名婴儿与75名服用阿莫西林但未接触秋水仙碱的匹配对照组母亲及其76名哺乳婴儿进行了比较。电话随访发生在初次询问后6到48个月（平均28个月）。在秋水仙碱暴露组中，76%的婴儿是纯母乳喂养的，平均母乳喂养持续时间为9.1个月。与对照婴儿相比，没有发现秋水仙碱暴露婴儿出现不良影响的增加风险。特别是，在胃肠道症状、生长和发育参数方面没有差异。 报告了10名正在接受秋水仙碱治疗的哺乳母亲。她们中没有一人出现任何病理报告。 一名妇女在怀孕和产后期间接受阿那白滞素100毫克皮下注射和口服秋水仙碱1毫克每天两次治疗家族性地中海热，同时哺乳她的婴儿（程度未指定）。在9个月大时，婴儿的发育在正常范围内。婴儿的常规疫苗接种计划正在按时进行，婴儿没有感染史。 ◉ 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:Long-term prophylactic maternal doses of colchicine up to 1.5 mg daily produce levels in milk that result in the infant receiving less than 10% of the maternal weight-adjusted dosage. The highest milk levels occur 2 to 4 hours after a dose, so avoiding breastfeeding during this time can minimize the infant dose, although some clinicians simply recommend taking the drug after nursing. No adverse effects in breastfed infants have been reported in case series and a case-control study and many experts and professional guidelines consider colchicine safe during breastfeeding in women being treated for familial Mediterranean fever or rheumatic conditions. ◉ Effects in Breastfed Infants:In 4 infants whose mothers were taking 1 to 1.5 mg of colchicine daily prophylactically for familial Mediterranean fever, no apparent effects were noted on clinical follow-up over at least 10 months. The authors also reported that they recalled another 6 women who breastfed their infants for at least 3 months during colchicine therapy (dosage not stated) and follow-up for at least 2 years revealed no clinical or developmental problems. An infant was breastfed (extent not stated) for 6 months during maternal intake of colchicine 0.6 mg twice daily. No apparent adverse effects were noted. In a study of mothers who took colchicine during pregnancy, 111 of 181 mothers reported breastfeeding (extent not stated) their infants. None of the infants reportedly had colchicine-related adverse effects. A case-control study compared 37 women who took colchicine during breastfeeding their 38 infants to a matched control group of 75 mothers who had taken amoxicillin, but were unexposed to colchicine, and their 76 breastfed infants. Telephone follow-up occurred at 6 to 48 months (average 28 months) after the initial inquiry. Among the colchicine-exposed group, 76% of infants were exclusively breastfed and the mean overall duration of breastfeeding was 9.1 months. No increased risk of adverse effects was noted in the colchicine-exposed infants compared to the control infants. Specifically, no differences in gastrointestinal symptoms, or growth and development parameters were seen. Ten nursing mothers who were being treated with colchicine were reported. None of them had any pathology reported. A woman was treated with anakinra 100 mg subcutaneously and oral colchicine 1 mg twice daily during pregnancy and postpartum for familial Mediterranean fever while she breastfed her infant (extent not specified). At 9 months of age, the infant’s development was within normal range. The routine vaccination schedule for the baby was being performed on time and there was no history of infection in the infant. ◉ Effects on Lactation and Breastmilk:Rel