Formoterol is metabolized primarily by direct glucuronidation at either the phenolic or aliphatic hydroxyl group and O-demethylation followed by glucuronide conjugation at either phenolic hydroxyl groups. Minor pathways involve sulfate conjugation of formoterol and deformylation followed by sulfate conjugation. The most prominent pathway involves direct conjugation at the phenolic hydroxyl group. The second major pathway involves O-demethylation followed by conjugation at the phenolic 2'-hydroxyl group. Four cytochrome P450 isozymes (CYP2D6, CYP2C19, CYP2C9 and CYP2A6) are involved in the O-demethylation of formoterol. Formoterol did not inhibit CYP450 enzymes at therapeutically relevant concentrations. Some patients may be deficient in CYP2D6 or 2C19 or both. Whether a deficiency in one or both of these isozymes results in elevated systemic exposure to formoterol or systemic adverse effects has not been adequately explored.
Formoterol was conjugated to inactive glucuronides and a previously unidentified sulfate. The phenol glucuronide of formoterol was the main metabolite in urine. Formoterol was also O-demethylated and deformylated. Plasma exposure to these pharmacologically active metabolites was low. O-demethylated formoterol was seen mainly as inactive glucuronide conjugates and deformylated formoterol only as an inactive sulfate conjugate. Intact formoterol and O-demethylated formoterol dominated recovery in feces. Mean recovery of unidentified metabolites was 7. 0% in urine and 2.0% in feces.
◉ Summary of Use during Lactation:Although no published data exist on the use of formoterol by 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 and an expert panel 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 formoterol?
Formoterol (also called eformoterol) is a medication used for the treatment of asthma and chronic obstructive pulmonary disease (COPD). It is in a class of medications called long-acting beta2-agonists. Beta2-agonists are bronchodilators. Bronchodilators help to open the airways in the lungs. Formoterol is taken by inhalation (breathing it in). It is usually used in combination with an inhaled corticosteroid for asthma treatment. For information about inhaled corticosteroids, see the MotherToBaby fact sheet at https://mothertobaby.org/fact-sheets/inhaled-corticosteroids-icss-pregnancy/pdf/. Formoterol can be found in some combination medications such as Symbicort® and Dulera®.
◈ I take formoterol. Can it make it harder for me to get pregnant?
Studies have not been done to see if formoterol could make it harder for a woman to get pregnant.
◈ I just found out that I am pregnant. Should I stop using my formoterol inhaler?
Talk with your healthcare providers before making any changes to your medication(s). It is important to consider the benefits of controlling asthma symptoms during pregnancy. Untreated asthma increases the chance for complications for both the pregnant woman and the baby. For more information about asthma, please see the MotherToBaby fact sheet at https://mothertobaby.org/fact-sheets/asthma-and-pregnancy/pdf/.If a woman’s asthma is well-controlled with formoterol prior to pregnancy, it is considered appropriate to continue its use during pregnancy if needed. When formoterol is inhaled, very limited amounts of the drug enter the blood, and even less is thought to reach the developing baby.
◈ Does taking formoterol increase the chance for miscarriage?
Miscarriage can occur in any pregnancy. There are no published studies looking at whether formoterol increases the chance of miscarriage.
◈ Can taking formoterol increase the chance of birth defects?
In every pregnancy, a woman starts out with a 3-5% chance of having a baby with a birth defect. This is called her background risk.There is limited data on the use of formoterol during pregnancy. The information from case reports did not suggest an increased chance of harm. A study on the use of long acting beta2-agonists (LABA) reported an increased chance for heart defects when used in the first trimester. However, these results are not conclusive since the pregnant woman’s underlying condition and severity of her asthma symptoms could have influenced the results. While more data is needed on formoterol, it is commonly used during pregnancy in combination with inhaled corticosteroids when asthma symptoms are severe enough to require treatment.
◈ Can taking formoterol during pregnancy cause other pregnancy complications?
One report of 33 women who used formoterol during pregnancy described five cases of birth before 37 weeks of pregnancy (preterm delivery). Three cases of preterm delivery would be expected due to the background risk. Another study compared 162 formoterol-exposed pregnancies to another long acting beta agonist and did not find a difference in birth weight, gestational age or chance of preterm delivery. It is unlikely that the chance for preterm delivery was increased by the use of formoterol during pregnancy. There may be a relationship between preterm delivery and poorly controlled or more severe asthma in pregnancy.
◈ Does taking formoterol in pregnancy cause long-term problems in behavior or learning for the baby?
There are not enough studies on formoterol to know whether there is a chance for long-term problems.
◈ Can I take formoterol while breastfeeding?
There have not been any studies on women taking formoterol while breastfeeding. Information on the use of related medications suggest that the use of a formoterol inhaler would be unlikely to result in high enough levels in the woman’s bloodstream to pass into breast milk in large amounts. Inhaled bronchodilators are generally considered acceptable for use during breastfeeding. Be sure to talk to your healthcare provider about all of your breastfeeding questions.
◈ If a man takes formoterol, could it affect his fertility (ability to get partner pregnant) or increase the chance of birth defects?
There are no data to suggest a man’s use of formoterol at the time of conception increases the chance for infertility or birth defects. In general, exposures that fathers have are unlikely to increase risks to a pregnancy. For more information, please see the MotherToBaby fact sheet Paternal Exposures at https://mothertobaby.org/fact-sheets/paternal-exposures-pregnancy/pdf/.
Concomitant treatment /with monoamine oxidase inhibitors, including furazolidine and procarbazine/ may prolong the QTc interval and increase the risk of ventricular arrhythmias; may increase chance of hypertensive reactions.
来源:Hazardous Substances Data Bank (HSDB)
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可能会增加接受卤代烃类麻醉药物患者的心律失常风险。
May increase risk of arrhythmias in patients receiving halogenated hydrocarbon anesthesia.
Concomitant treatment /with tricyclic antidepressants, disopyramide, phenothiazines, procainamide or quinidine/may prolong the QTc interval and increase the risk of ventricular arrhythmias.
In asthma patients following a 12 or 24 ug dose: 10% and 15 to 18% excreted unchanged in the urine, respectively. In chronic obstructive pulmonary disease (COPD) patients following a 12 or 24 ug dose: 7% and 6 to 9% excreted unchanged in the urine; respectively.
Section 1. Chemical Product and Company Identification Formoterol Common Name/ Trade Name Formoterol Section 4. First Aid Measures Eye Contact Check for and remove any contact lenses. In case of contact, immediately flush eyes with plenty of water for at least 15 minutes. Get medical attention if irritation occurs. Skin Contact Wash with soap and water. Cover the irritated skin with an emollient. Get medical attention if irritation develops. Serious Skin Contact Not available. Inhalation If inhaled, remove to fresh air. If not breathing, give artificial respiration. If breathing is difficult, give oxygen. Get medical attention. Serious Inhalation Not available. Ingestion Do NOT induce vomiting unless directed to do so by medical personnel. Never give anything by mouth to an unconscious person. If large quantities of this material are swallowed, call a physician immediately. Loosen tight clothing such as a collar, tie, belt or waistband. Serious Ingestion Not available. Section 5. Fire and Explosion Data Flammability of the Product May be combustible at high temperature. Auto-Ignition Temperature Not available. Flash Points Not available. Flammable Limits Not available. Products of Combustion These products are carbon oxides (CO, CO2), nitrogen oxides (NO, NO2...). Fire Hazards in Presence of Slightly flammable to flammable in presence of heat. Various Substances Explosion Hazards in Presence Risks of explosion of the product in presence of mechanical impact: Not available. Slightly explosive in presence of open flames and sparks. of Various Substances SMALL FIRE: Use DRY chemical powder. Fire Fighting Media and Instructions LARGE FIRE: Use water spray, fog or foam. Do not use water jet. As with most organic solids, fire is possible at elevated temperatures Special Remarks on Fire Hazards Special Remarks on Explosion Fine dust dispersed in air in sufficient concentrations, and in the presence of an ignition source is a potential dust Hazards explosion hazard. Section 6. Accidental Release Measures Small Spill Use appropriate tools to put the spilled solid in a convenient waste disposal container. Finish cleaning by spreading water on the contaminated surface and dispose of according to local and regional authority requirements. Large Spill Use a shovel to put the material into a convenient waste disposal container. Finish cleaning by spreading water on the contaminated surface and allow to evacuate through the sanitary system. Formoterol Section 7. Handling and Storage Precautions Keep away from heat. Keep away from sources of ignition. Ground all equipment containing material. Do not breathe dust. Keep away from incompatibles such as oxidizing agents. Storage Keep container tightly closed. Keep container in a cool, well-ventilated area. Section 8. Exposure Controls/Personal Protection Engineering Controls Use process enclosures, local exhaust ventilation, or other engineering controls to keep airborne levels below recommended exposure limits. If user operations generate dust, fume or mist, use ventilation to keep exposure to airborne contaminants below the exposure limit. Personal Protection Safety glasses. Lab coat. Dust respirator. Be sure to use an approved/certified respirator or equivalent. Gloves. Personal Protection in Case of Splash goggles. Full suit. Dust respirator. Boots. Gloves. A self contained breathing apparatus should be used a Large Spill to avoid inhalation of the product. Suggested protective clothing might not be sufficient; consult a specialist BEFORE handling this product. Exposure Limits Not available. Section 9. Physical and Chemical Properties Physical state and appearance Solid. (Powdered solid.) Odor Not available. Taste Not available. Molecular Weight 344.41 g/mole Color White to yellowish. pH (1% soln/water) Not applicable. Boiling Point Not available. Melting Point Not available. Critical Temperature Not available. Not available. Specific Gravity Vapor Pressure Not applicable. Vapor Density Not available. Volatility Not available. Odor Threshold Not available. Not available. Water/Oil Dist. Coeff. Ionicity (in Water) Not available. Not available. Dispersion Properties Solubility Insoluble in cold water. Soluble in Dimethyl Sulfoxide (DMSO). The solubility in DMSO is 20 mg/ml Section 10. Stability and Reactivity Data Stability The product is stable. Instability Temperature Not available. Conditions of Instability Not available. Incompatibility with various Reactive with oxidizing agents. substances Corrosivity Not available. Formoterol Not available. Special Remarks on Reactivity Not available. Special Remarks on Corrosivity Polymerization Will not occur. Section 11. Toxicological Information Routes of Entry Inhalation. Ingestion. Toxicity to Animals LD50: Not available. LC50: Not available. Chronic Effects on Humans May cause damage to the following organs: cardiovascular system, upper respiratory tract. Other Toxic Effects on Slightly hazardous in case of skin contact (irritant), of ingestion, of inhalation. Humans Special Remarks on Not available. Toxicity to Animals Special Remarks on Not available. Chronic Effects on Humans Special Remarks on other Acute Potential Health Effects: Toxic Effects on Humans Skin: May cause skin irritation. Eyes: May cause eye irritation. Inhalation: May cause respiratory tract irritation, dry mouth, nausea. May affect cardiovascular system(angina, arrhythmias, hypertension, hypotension, palpitations, tachydcardia), respiration (may lead to paradoxical bronchospasm). It may also affect behavior/central nervous system (dizziness, fatigue, headache, tremors, insomnia, malaise, nervousness), metabolism (hyperglycemia, metabolic acidosis. May cause allergic reaction (anaphylaxis) Ingestion: May cause dry mouth, nausea. It is expected to be a low hazard during usual industrial handling. Chronic Potential Health Effects: Inhalation: Prolonged or repeated overexposure by inhalation may affect respiration (bronchiolar dilation, paradoxical bronchospasm), cardiovascular system (increased pulse rate and other symptoms similar to acute inhalation). It may cause allergic reaction (anaphylaxis). Medical Conditions Aggravated by Exposure: Hypersensitivity to material, acute attack of asthma, cardiovascular disease (including agina, hypertension), Diabetes, Glaucoma, Hyperthyroidism, Pheochromocytoma. Section 12. Ecological Information Not available. Ecotoxicity BOD5 and COD Not available. Products of Biodegradation Possibly hazardous short term degradation products are not likely. However, long term degradation products may arise. The product itself and its products of degradation are not toxic. Toxicity of the Products of Biodegradation Special Remarks on the Not available. Products of Biodegradation Section 13. Disposal Considerations Waste Disposal Waste must be disposed of in accordance with federal, state and local environmental control regulations. Formoterol Section 14. Transport Information DOT Classification Not a DOT controlled material (United States). Identification Not applicable. Not applicable. Special Provisions for Transport DOT (Pictograms) Section 15. Other Regulatory Information and Pictograms No products were found. Federal and State Regulations California California prop. 65: This product contains the following ingredients for which the State of California has found to cause cancer which would require a warning under the statute: No products were found. Proposition 65 Warnings California prop. 65: This product contains the following ingredients for which the State of California has found to cause birth defects which would require a warning under the statute: No products were found. Other Regulations Not available. Other Classifications WHMIS (Canada) Not controlled under WHMIS (Canada). DSCL (EEC) This product is not classified according Not applicable. to the EU regulations. Health Hazard HMIS (U.S.A.) 1 National Fire Protection 1 Flammability 1 Association (U.S.A.) Fire Hazard 1 0 Reactivity Health Reactivity 0 Specific hazard Personal Protection E WHMIS (Canada) (Pictograms) DSCL (Europe) (Pictograms) TDG (Canada) (Pictograms) ADR (Europe) (Pictograms) Formoterol Protective Equipment Gloves. Lab coat. Dust respirator. Be sure to use an approved/certified respirator or equivalent.
[EN] COMPOSITIONS AND METHODS OF REGULATING CANCER RELATED DISORDERS AND DISEASES<br/>[FR] COMPOSITIONS ET MÉTHODES DE RÉGULATION DE TROUBLES ET MALADIES ASSOCIÉS AU CANCER
申请人：ONCO THERAPIES LLC
公开号：WO2017070052A1
公开（公告）日：2017-04-27
Provided herein are naphthylic derivative compounds, or pharmaceutically acceptable salts thereof, that are useful for inhibiting cancers. Also provided herein are methods of using effective amounts of said compounds, optionally with pharmaceutical carriers, for the treatment of cancers within human subjects.
Bronchodilating compositions and methods are provided. The compositions are intended for administration as a nebulized aerosol. In certain embodiments, the compositions contain formoterol, or a derivative thereof. Methods for treatment, prevention, or amelioration of one or more symptoms of bronchoconstrictive disorders using the compositions provided herein are also provided.
NMR characterisation of structure in solvates and polymorphs of formoterol fumarate
作者：David C. Apperley、A. Fraser Markwell、Robin K. Harris、Paul Hodgkinson
DOI：10.1002/mrc.3862
日期：2012.10
The solid-state structures of two polymorphs and two alcoholates (ethanol and isopropanol) of formoterolfumarate have been investigated by a combination of NMR techniques. First-principles shielding computations are combined with NMR data to successfully relate peaks to their crystallographic positions for the solvates, including atoms that are in equivalent molecular positions. The uncharacterised
Active agent delivery systems and methods for protecting and administering active agents
申请人：Mickle Travis
公开号：US20070232529A1
公开（公告）日：2007-10-04
The present invention relates to active agent delivery systems and more specifically to compositions that comprise amino acids, as single amino acids or peptides, covalently attached to active agents and methods for administering conjugated active agent compositions.
The invention provides a pharmaceutical product, kit or composition comprising a first active ingredient which is a P2X
7
receptor antagonist, and a second active ingredient which is a corticosteroid, of use in the treatment of respiratory diseases such as chronic obstructive pulmonary disease and asthma.
