Pregna-1,4-diene-3,20-dione, 9-fluoro-11,17,21-trihydroxy-16-methyl-, (11beta,16alpha)-

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 类固醇和类固醇衍生物
• 英文名称: Pregna-1,4-diene-3,20-dione, 9-fluoro-11,17,21-trihydroxy-16-methyl-, (11beta,16alpha)-
• 英文别名: (9S,11S,16R)-9-fluoro-11,17-dihydroxy-17-(2-hydroxyacetyl)-10,13,16-trimethyl-6,7,8,11,12,14,15,16-octahydrocyclopenta[a]phenanthren-3-one
• 化学式: C₂₂H₂₉FO₅
• 分子量: 392.5
• InChiKey: UREBDLICKHMUKA-CIYZRDELSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  28
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.73
• 拓扑面积：
  94.8
• 氢给体数：
  3
• 氢受体数：
  6

ADMET

毒理性

• 在妊娠和哺乳期间的影响

哺乳期使用概要：外用皮质类固醇尚未在哺乳期进行过研究。由于只有大量使用最强效的皮质类固醇才会对母亲产生系统性影响，因此短期外用皮质类固醇不太可能通过进入母乳而对哺乳婴儿构成风险。然而，最好还是使用最弱效的药物，并且尽可能在最小的皮肤面积上使用。特别重要的是确保婴儿的皮肤不直接接触到涂抹了药物的区域。只有低效皮质类固醇（例如，氢化可的松，曲安奈德）应该用在乳头或乳晕上，因为婴儿可能会直接从皮肤上摄入药物。只有水溶性乳膏或凝胶产品应该涂抹在乳房上，因为软膏可能会使婴儿通过舔舐接触到高水平的矿脂。如果外用皮质类固醇涂在乳房或乳头区域，哺乳前应彻底擦掉。 由于眼部吸收有限，眼科使用的外用皮质类固醇，包括眼内植入物，预计不会对哺乳婴儿造成任何不良影响。为了大幅减少使用眼药水后药物到达母乳的量，可以在眼角处对泪囊施加压力1分钟或更长时间，然后用吸收性纸巾去除多余的溶液。 对哺乳婴儿的影响：母亲乳头外用具有相对较高盐皮质激素活性的皮质类固醇（异氟泼尼松醋酸酯）导致其2个月大的哺乳婴儿出现QT间期延长、库欣综合征外貌、严重高血压、生长减缓和电解质异常。这位母亲从婴儿出生起就因乳头疼痛而使用该乳膏。 对泌乳和母乳的影响：截至修订日期，未找到相关已发布信息。

◉ Summary of Use during Lactation:Topical dexamethasone has not been studied during breastfeeding. Since only extensive application of the most potent corticosteroids cause systemic effects in the mother, it is unlikely that short-term application of topical corticosteroids would pose a risk to the breastfed infant by passage into breastmilk. However, it would be prudent to use the least potent drug on the smallest area of skin possible. It is particularly important to ensure that the infant's skin does not come into direct contact with the areas of skin that have been treated. Only the lower potency corticosteroids (e.g., hydrocortisone, triamcinolone) should be used on the nipple or areola where the infant could directly ingest the drugs from the skin. Only water-miscible cream or gel products should be applied to the breast because ointments may expose the infant to high levels of mineral paraffins via licking. Any topical corticosteroid should be wiped off thoroughly prior to nursing if it is being applied to the breast or nipple area. Because absorption from the eye is limited, ophthalmic dexamethasone, including ocular inserts, would not be expected to cause any adverse effects in breastfed infants. To substantially diminish the amount of drug that reaches the breastmilk after using eye drops, place pressure over the tear duct by the corner of the eye for 1 minute or more, then remove the excess solution with an absorbent tissue. ◉ Effects in Breastfed Infants:Topical application of a corticosteroid with relatively high mineralocorticoid activity (isofluprednone acetate) to the mother's nipples resulted in prolonged QT interval, cushingoid appearance, severe hypertension, decreased growth and electrolyte abnormalities in her 2-month-old breastfed infant. The mother had used the cream since birth for painful nipples. ◉ 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

哺乳期使用总结：因为没有关于哺乳期间系统性使用地塞米松的信息，可能更倾向于选择另一种皮质类固醇，特别是在哺乳新生儿或早产儿时。局部注射，例如用于腱炎的，不会预期对哺乳婴儿造成任何不良影响，但偶尔可能导致暂时性的乳汁供应减少。另见地塞米松，外用。 对哺乳婴儿的影响：没有报告任何皮质类固醇有影响。 对泌乳和母乳的影响：地塞米松可以导致非哺乳妇女的基础血清催乳素和促甲状腺激素释放激素刺激的血清催乳素增加下降。截至修订日期，没有找到关于地塞米松对哺乳母亲血清催乳素或泌乳影响的已发布信息。然而，有报道称，将中到大剂量的储库型皮质类固醇注射到关节中会导致暂时性的泌乳减少。 一项对46位在34周前分娩的妇女的研究发现，如果在分娩前3到9天内给予另一种皮质类固醇（倍他米松，两次肌肉注射，每次11.4毫克，间隔24小时），会导致哺乳II期延迟，并且在分娩后10天内的平均乳汁量减少。如果婴儿在母亲接受皮质类固醇后不到3天或多于10天分娩，乳汁量不会受到影响。等效剂量的地塞米松可能会有同样的效果。 一项对87位孕妇的研究发现，孕期给予上述剂量的倍他米松会导致孕期过早刺激乳糖分泌。尽管增加在统计学上显著，但临床重要性似乎很小。等效剂量的地塞米松可能会有同样的效果。

◉ Summary of Use during Lactation:Because no information is available on the use of systemic dexamethasone during breastfeeding, an alternate corticosteroid may be preferred, especially while nursing a newborn or preterm infant. Local injections, such as for tendinitis, would not be expected to cause any adverse effects in breastfed infants, but might occasionally cause temporary loss of milk supply. See also Dexamethasone, Topical. ◉ Effects in Breastfed Infants:None reported with any corticosteroid. ◉ Effects on Lactation and Breastmilk:Dexamethasone can cause a decrease in basal serum prolactin and thyrotropin-releasing hormone stimulated serum prolactin increase in nonnursing women. Published information on the effects of dexamethasone on serum prolactin or on lactation in nursing mothers was not found as of the revision date. However, medium to large doses of depot corticosteroids injected into joints have been reported to cause temporary reduction of lactation. A study of 46 women who delivered an infant before 34 weeks of gestation found that a course of another corticosteroid (betamethasone, 2 intramuscular injections of 11.4 mg of betamethasone 24 hours apart) given between 3 and 9 days before delivery resulted in delayed lactogenesis II and lower average milk volumes during the 10 days after delivery. Milk volume was not affected if the infant was delivered less than 3 days or more than 10 days after the mother received the corticosteroid. An equivalent dosage regimen of dexamethasone might have the same effect. A study of 87 pregnant women found that betamethasone given as above during pregnancy caused a premature stimulation of lactose secretion during pregnancy. Although the increase was statistically significant, the clinical importance appears to be minimal. An equivalent dosage regimen of dexamethasone might have the same effect.

来源:Drugs and Lactation Database (LactMed)