Salbutamol is not metabolized in the lung but is converted in the liver to the 4'-o-sulphate (salbutamol 4'-O-sulfate) ester, which has negligible pharmacologic activity. It may also be metabolized by oxidative deamination and/or conjugation with glucuronide. Salbutamol is ultimately excreted in the urine as free drug and as the metabolite.
Metabolized through sulfate conjugation to its inactive 4'-O-sulfate ester by phenol sulphotransferase (PST). The (R)-enantiomer of albuterol is preferentially metabolized (ten fold) by PST compared to the (S)-enantiomer of albuterol.
Hydrolyzed by esterases in tissue and blood to the active compound colterol. The drug is also conjugatively metabolized to salbutamol 4'-O-sulfate.
Route of Elimination: Approximately 72% of the inhaled dose is excreted in the urine within 24 hours, 28% as unchanged drug and 44% as metabolite.
Half Life: 1.6 hours
Salbutamol is a beta(2)-adrenergic agonist and thus it stimulates beta(2)-adrenergic receptors. Binding of albuterol to beta(2)-receptors in the lungs results in relaxation of bronchial smooth muscles. It is believed that salbutamol increases cAMP production by activating adenylate cyclase, and the actions of salbutamol are mediated by cAMP. Increased intracellular cyclic AMP increases the activity of cAMP-dependent protein kinase A, which inhibits the phosphorylation of myosin and lowers intracellular calcium concentrations. A lowered intracellular calcium concentration leads to a smooth muscle relaxation and bronchodilation. In addition to bronchodilation, salbutamol inhibits the release of bronchoconstricting agents from mast cells, inhibits microvascular leakage, and enhances mucociliary clearance.
参考文献：M Chen, V Vijay, Q Shi, Z Liu, H Fang, W Tong. 美国食品药品监督管理局批准的药物标签用于研究药物诱导的肝损伤，《药物发现今日》，16(15-16):697-703, 2011. PMID:21624500 DOI:10.1016/j.drudis.2011.05.007
M Chen, A Suzuki, S Thakkar, K Yu, C Hu, W Tong. DILIrank：按人类发展药物诱导肝损伤风险排名的最大参考药物清单。《药物发现今日》2016, 21(4): 648-653. PMID:26948801 DOI:10.1016/j.drudis.2016.02.015
References:M Chen, V Vijay, Q Shi, Z Liu, H Fang, W Tong. FDA-Approved Drug Labeling for the Study of Drug-Induced Liver Injury, Drug Discovery Today, 16(15-16):697-703, 2011. PMID:21624500 DOI:10.1016/j.drudis.2011.05.007
M Chen, A Suzuki, S Thakkar, K Yu, C Hu, W Tong. DILIrank: the largest reference drug list ranked by the risk for developing drug-induced liver injury in humans. Drug Discov Today 2016, 21(4): 648-653. PMID:26948801 DOI:10.1016/j.drudis.2016.02.015
Following inhalation, salbutamol acts topically on bronchial smooth muscle and the drug is initially undetectable in the blood. After 2 to 3 hours low concentrations are seen, due presumably to the portion of the dose which is swallowed and absorbed in the gut. In particular, the systemic levels of salbutamol are low after inhalation of recommended doses. A trial conducted in 12 healthy male and female subjects using a higher dose (1,080 mcg of albuterol base) showed that mean peak plasma concentrations of approximately 3 ng/mL occurred after dosing when salbutamol was delivered using propellant HFA-134a. The mean time to peak concentrations (Tmax) was delayed after administration of VENTOLIN (salbutamol) HFA (Tmax = 0.42 hours) as compared with CFC-propelled salbutamol inhaler (Tmax = 0.17 hours).
After oral administration, 58-78% of the dose is excreted in the urine in 24 hours, approximately 60% as metabolites. A small fraction is excreted in the feces.
来源:DrugBank
吸收、分配和排泄
分布容积
静脉给药的沙丁胺醇的分布容积已记录为156 +/- 38升。
The volume of distribution recorded for intravenously administered salbutamol has been recorded as 156 +/- 38 L.
The renal clearance of salbutamol has been documented as 272 +/- 38 ml/min after oral administration and 291 +/- 70 ml/min after intravenous administration. Furthermore, the renal clearance of the predominant sulfate conjugate metabolite was recorded as 98.5 +/- 23.5 ml/min following oral administration.
来源:DrugBank
吸收、分配和排泄
消除：肾脏，69%至90%（60%为代谢物）。粪便，4%。
Elimination: Renal, 69 to 90% (60% as the metabolite). Fecal, 4%.
Section 1. Chemical Product and Company Identification Albuterol Catalog AL155 Common Name/ Number(s). Trade Name CAS# 18559-94-9 Manufacturer RTECS SJ7450000 SPECTRUM QUALITY PRODUCTS INC. TSCA TSCA 8(b) inventory: No products were found. Commercial Name(s) Salbutamol CI# Not available. Synonym alpha'-[[(1,1-Dimethyl)amino]methyl]-4-hydroxy-1,3-benzenedimethanol IN CASE OF EMERGENCY Chemical Name Chemical Family Not available. CALL (310) 516-8000 C13H21NO3 Chemical Formula SPECTRUM QUALITY PRODUCTS INC. Section 2.Composition and Information on Ingredients Exposure Limits TWA (mg/m3) STEL (mg/m3) CEIL (mg/m3) Name CAS # % by Weight 1) Albuterol 18559-94-9 100 Toxicological Data Albuterol on Ingredients LD50: Not available. LC50: Not available. Section 3. Hazards Identification Potential Acute Health Effects Hazardous in case of eye contact (irritant), of ingestion. Slightly hazardous in case of skin contact (irritant), of inhalation. Potential Chronic Health CARCINOGENIC EFFECTS: Not available. Effects MUTAGENIC EFFECTS: Not available. TERATOGENIC EFFECTS: Not available. DEVELOPMENTAL TOXICITY: Not available. The substance is toxic to lungs, mucous membranes. Repeated or prolonged exposure to the substance can produce target organs damage. Albuterol 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. 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 Not available. Various Substances Explosion Hazards in Presence Risks of explosion of the product in presence of mechanical impact: Not available. Risks of explosion of the product in presence of static discharge: Not available. 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. Not available. Special Remarks on Fire Hazards Special Remarks on Explosion Not available. Hazards 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. Albuterol Section 7. Handling and Storage Precautions Keep away from heat. Keep away from sources of ignition. Empty containers pose a fire risk, evaporate the residue under a fume hood. Ground all equipment containing material. Do not breathe dust. Avoid contact with eyes. Wear suitable protective clothing. If you feel unwell, seek medical attention and show the label when possible. 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 Splash goggles. 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. Odor Not available. Not available. Taste Molecular Weight 239.32 g/mole Not available. Color Not available. pH (1% soln/water) Boiling Point Decomposes. Melting Point 151°C (303.8°F) Critical Temperature Not available. Specific Gravity Not available. Not applicable. Vapor Pressure Vapor Density Not available. Not available. Volatility Odor Threshold Not available. Water/Oil Dist. Coeff. Not available. Ionicity (in Water) Not available. Dispersion Properties Not available. Solubility Not available. Section 10. Stability and Reactivity Data Stability The product is stable. Instability Temperature Not available. Conditions of Instability Not available. Incompatibility with various Not available. substances Corrosivity Non-corrosive in presence of glass. Albuterol Special Remarks on Not available. Reactivity Special Remarks on Not available. Corrosivity Polymerization Will not occur. Section 11. Toxicological Information Routes of Entry Eye contact. Ingestion. Toxicity to Animals LD50: Not available. LC50: Not available. Chronic Effects on Humans Causes damage to the following organs: lungs, mucous membranes. Other Toxic Effects on Hazardous in case of ingestion. Humans Slightly hazardous in case of skin contact (irritant), of inhalation. Special Remarks on Not available. Toxicity to Animals Special Remarks on Passes through the placental barrier in human. Chronic Effects on Humans Special Remarks on other Not available. Toxic Effects on Humans Section 12. Ecological Information Ecotoxicity Not available. BOD5 and COD Not available. Products of Biodegradation Possibly hazardous short term degradation products are not likely. However, long term degradation products may arise. Toxicity of the Products The products of degradation are more toxic. of Biodegradation Special Remarks on the Not available. Products of Biodegradation Section 13. Disposal Considerations Waste Disposal Section 14. Transport Information DOT Classification Not a DOT controlled material (United States). Identification Not applicable. Special Provisions for Not applicable. Transport DOT (Pictograms) Albuterol Section 15. Other Regulatory Information and Pictograms No products were found. Federal and State Regulations California Proposition 65 Warnings Other Regulations OSHA: Hazardous by definition of Hazard Communication Standard (29 CFR 1910.1200). WHMIS (Canada) CLASS D-2A: Material causing other toxic effects (VERY TOXIC). Other Classifications DSCL (EEC) R36- Irritating to eyes. Health Hazard HMIS (U.S.A.) 2 National Fire Protection 1 Flammability 1 Association (U.S.A.) Fire Hazard 2 0 Reactivity Health Reactivity 0 Specific hazard Personal Protection E WHMIS (Canada) (Pictograms) DSCL (Europe) (Pictograms) TDG (Canada) (Pictograms) ADR (Europe) (Pictograms) Protective Equipment Gloves. Lab coat. Dust respirator. Be sure to use an approved/certified respirator or equivalent. Wear appropriate respirator when ventilation is inadequate. Splash goggles.
[EN] ACC INHIBITORS AND USES THEREOF<br/>[FR] INHIBITEURS DE L'ACC ET UTILISATIONS ASSOCIÉES
申请人：GILEAD APOLLO LLC
公开号：WO2017075056A1
公开（公告）日：2017-05-04
The present invention provides compounds I and II useful as inhibitors of Acetyl CoA Carboxylase (ACC), compositions thereof, and methods of using the same.
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.
The present invention provides a cobalamin-drug conjugate suitable for the treatment of tumor related diseases. Cobalamin is indirectly covalently bound to an anti-tumor drug via a cleavable linker and one or more optional spacers. Cobalamin is covalently bound to a first spacer or the cleavable linker via the 5′-OH of the cobalamin ribose ring. The drug is bound to a second spacer of the cleavable linker via an existing or added functional group on the drug. After administration, the conjugate forms a complex with transcobalamin (any of its isoforms). The complex then binds to a receptor on a cell membrane and is taken up into the cell. Once in the cell, an intracellular enzyme cleaves the conjugate thereby releasing the drug. Depending upon the structure of the conjugate, a particular class or type of intracellular enzyme affects the cleavage. Due to the high demand for cobalamin in growing cells, tumor cells typically take up a higher percentage of the conjugate than do normal non-growing cells. The conjugate of the invention advantageously provides a reduced systemic toxicity and enhanced efficacy as compared to a corresponding free drug.
