Salmeterol xinafoate oral inhalation aerosol or oral inhalation powder (Serevent Diskus) is stable for 2 years or 18 months, respectively, from the date of manufacture.
... The cytochrome P450 (CYP) isoform 3A4 is responsible for aliphatic oxidation of salmeterol base, which is extensively metabolised by hydroxylation with the major metabolite being alpha-hydroxysalmeterol, with subsequent elimination predominantly in the feces...
来源:Hazardous Substances Data Bank (HSDB)
代谢
肝脏代谢，通过CYP3A4羟基化
半衰期：5.5小时
Hepatic, metabolized by hydroxylation via CYP3A4
Half Life: 5.5 hours
Salmeterol's long, lipophilic side chain binds to exosites near beta(2)-receptors in the lungs and on bronchiolar smooth muscle, allowing the active portion of the molecule to remain at the receptor site, continually binding and releasing. Beta(2)-receptor stimulation in the lung causes relaxation of bronchial smooth muscle, bronchodilation, and increased bronchial airflow.
来源:Toxin and Toxin Target Database (T3DB)
毒理性
致癌物分类
对人类不具有致癌性（未被国际癌症研究机构IARC列名）。
No indication of carcinogenicity to humans (not listed by IARC).
◉ Summary of Use during Lactation:Although no published data exist on the use of salmeterol by mouth or inhaler during lactation, data from the related drug, terbutaline, indicate that very little is expected to be excreted into breastmilk. The authors of several reviews agree that use of inhaled bronchodilators is acceptable during breastfeeding because of the low bioavailability and maternal serum levels after use.
◉ Effects in Breastfed Infants:Relevant published information was not found as of the revision date.
◉ Effects on Lactation and Breastmilk:Relevant published information was not found as of the revision date.
◈ What is salmeterol?
Salmeterol is a medication that has been used for the treatment of asthma and chronic obstructive pulmonary disease (COPD). It is in a class of medications called beta2-agonists. Beta2-agonists help to open the airways in the lungs (bronchodilators). Salmeterol is a long-acting beta2-agonist taken by breathing it into the lungs (inhalation). It is used together with an inhaled corticosteroid to treat asthma. For information on inhaled corticosteroids, see the MotherToBaby fact sheet at https://mothertobaby.org/fact-sheets/inhaled-corticosteroids-icss-pregnancy/.Sometimes when people find out they are pregnant, they think about changing how they take their medication, or stopping their medication altogether. However, it is important to talk with your healthcare providers before making any changes to how you take this medication. Your healthcare providers can talk with you about the benefits of treating your condition and the risks of untreated illness during pregnancy.Salmeterol has been considered a medication of choice if long-acting beta agonist treatment is needed during pregnancy. If a person’s asthma was well-controlled with salmeterol before pregnancy, it may be recommended to continue using it during pregnancy.
◈ I take salmeterol. Can it make it harder for me to get pregnant?
It is not known if salmeterol can make it harder to get pregnant.
◈ Does taking salmeterol increase the chance for miscarriage?
Miscarriage can occur in any pregnancy. Studies have not been done to see if salmeterol could increase the chance of miscarriage. There are no reports that suggest an increased chance of miscarriage when salmeterol is used during pregnancy.
◈ Does taking salmeterol increase the chance of birth defects?
Every pregnancy starts out with a 3-5% chance of having a birth defect. This is called the background risk. A small number of studies do not suggest an increased chance of birth defects with the use of inhaled salmeterol during pregnancy. When salmeterol is inhaled, very little of the drug gets into the blood. Even less of the medication is expected to reach the developing baby.
◈ Does taking salmeterol in pregnancy increase the chance of other pregnancy-related problems?
Based on the studies reviewed, use of salmeterol during pregnancy is not expected to increases the chance for pregnancy complications. Small studies have not suggested higher rates of preterm delivery (babies born before 37 weeks) or low birth weight (weighting less than 5 pounds, 8 ounces [2500grams] at birth). However, asthma that is not well controlled can increase the chance for pregnancy complications. For information on asthma, see the MotherToBaby fact sheet at https://mothertobaby.org/fact-sheets/asthma-and-pregnancy/.
◈ Does taking salmeterol in pregnancy affect future behavior or learning for the child?
Studies have not been done to see if salmeterol can cause behavior or learning issues for the child. There are no reports of an increased chance of future behavior or learning problems in people who were exposed to salmeterol during pregnancy.
◈ Breastfeeding while taking salmeterol:
Studies have not been done to look at the use of salmeterol during breastfeeding. When salmeterol is inhaled, very little of the drug gets into the blood and it is not expected to pass into breastmilk in large amounts. Using inhaled bronchodilators is usually compatible with breastfeeding. Be sure to talk to your healthcare provider about all of your breastfeeding questions.
◈ If a male takes salmeterol, could it affect fertility (ability to get partner pregnant) or increase the chance of birth defects?
Studies have not been done to see if salmeterol could affect fertility or increase the chance of birth defects above the background risk. Using a salmeterol inhaler is not thought to cause high levels of the drug in a person’s bloodstream, so effects on fertility or a pregnancy are not expected. In general, exposures that fathers or sperm donors have are unlikely to increase the risks to a pregnancy. For more information, please see the MotherToBaby fact sheet Paternal Exposures at https://mothertobaby.org/fact-sheets/paternal-exposures-pregnancy/.
来源:Mother To Baby Fact Sheets
毒理性
暴露途径
由于治疗剂量较小，在吸入推荐剂量后，沙美特罗的系统水平较低或无法检测到。
Because of the small therapeutic dose, systemic levels of salmeterol are low or undetectable after inhalation of recommended doses.
Salmeterol is 57.4% eliminated in the feces and 23% in the urine. Less than 5% of a dose is eliminated in the urine as unchanged salmeterol.
来源:DrugBank
吸收、分配和排泄
分布容积
在哮喘患者中，中央室的分布容积为177升，而外周室的分布容积为3160升。
In asthmatic patients, the volume of distribution of the central compartment is 177L and the volume of distribution of the peripheral compartment is 3160L.
来源:DrugBank
吸收、分配和排泄
清除
在一组哮喘患者中，沙美特罗的平均清除率为392L/h。关于沙美特罗清除率的进一步数据不易获得。
The average clearance of salmeterol in a group of asthmatic patients was 392L/h. Further data regarding the clearance of salmeterol is not readily available.
The absorption of salmeterol xinafoate from the respiratory tract following oral inhalation has not been fully characterized. Although it has been suggested that most of an orally inhaled drug actually is swallowed, the bronchodilating action of orally inhaled sympathomimetic agents is believed to result from a local action of the portion of the dose that reaches the bronchial tree. Systemic concentrations of salmeterol are low or undetectable after inhalation of the recommended dosage of the aerosol (42 ug) or powder (50 ug) twice daily and are not predictive of therapeutic effects.
DISUBSTITUTED TRIFLUOROMETHYL PYRIMIDINONES AND THEIR USE
申请人：BAYER PHARMA AKTIENGESELLSCHAFT
公开号：US20160221965A1
公开（公告）日：2016-08-04
The present application relates to novel 2,5-disubstituted 6-(trifluoromethyl)pyrimidin-4(3H)-one derivatives, to processes for their preparation, to their use alone or in combinations for the treatment and/or prevention of diseases, and to their use for preparing medicaments for the treatment and/or prevention of diseases, in particular for treatment and/or prevention of cardiovascular, renal, inflammatory and fibrotic diseases.
[EN] S-NITROSOMERCAPTO COMPOUNDS AND RELATED DERIVATIVES<br/>[FR] COMPOSÉS DE S-NITROSOMERCAPTO ET DÉRIVÉS APPARENTÉS
申请人：GALLEON PHARMACEUTICALS INC
公开号：WO2009151744A1
公开（公告）日：2009-12-17
The present invention is directed to mercapto-based and S- nitrosomercapto-based SNO compounds and their derivatives, and their use in treating a lack of normal breathing control, including the treatment of apnea and hypoventilation associated with sleep, obesity, certain medicines and other medical conditions.
Compositions for Treatment of Cystic Fibrosis and Other Chronic Diseases
申请人：Vertex Pharmaceuticals Incorporated
公开号：US20150231142A1
公开（公告）日：2015-08-20
The present invention relates to pharmaceutical compositions comprising an inhibitor of epithelial sodium channel activity in combination with at least one ABC Transporter modulator compound of Formula A, Formula B, Formula C, or Formula D. The invention also relates to pharmaceutical formulations thereof, and to methods of using such compositions in the treatment of CFTR mediated diseases, particularly cystic fibrosis using the pharmaceutical combination compositions.
[EN] NOVEL COMPOUNDS AND PHARMACEUTICAL COMPOSITIONS THEREOF FOR THE TREATMENT OF INFLAMMATORY DISORDERS<br/>[FR] NOUVEAUX COMPOSÉS ET COMPOSITIONS PHARMACEUTIQUES LES COMPRENANT POUR LE TRAITEMENT DE TROUBLES INFLAMMATOIRES
申请人：GALAPAGOS NV
公开号：WO2017012647A1
公开（公告）日：2017-01-26
The present invention discloses compounds according to Formula (I), wherein R1, R3, R4, R5, L1, and Cy are as defined herein. The present invention also provides compounds, methods for the production of said compounds of the invention, pharmaceutical compositions comprising the same and their use in allergic or inflammatory conditions, autoimmune diseases, proliferative diseases, transplantation rejection, diseases involving impairment of cartilage turnover, congenital cartilage malformations, and/or diseases associated with hypersecretion of IL6 and/or interferons. The present invention also methods for the prevention and/or treatment of the aforementioned diseases by administering a compound of the invention.
The present invention relates compounds of the formula: or pharmaceutically acceptable salts thereof, useful as sodium channel blockers, as well as compositions containing the same, processes for the preparation of the same, and therapeutic methods of use therefore in promoting hydration of mucosal surfaces and the treatment of diseases including cystic fibrosis, chronic obstructive pulmonary disease, asthma, bronchiectasis, acute and chronic bronchitis, emphysema, and pneumonia.
