Oxybutynin is heavily metabolized by the CYP3A4 enzyme system in both the liver and the wall of the intestine. It undergoes first-pass metabolism, and its resulting primary active metabolite, N-desethyloxybutynin circulates. It is active at the muscarinic receptors in both the bladder and the salivary gland. Hepatic biotransformation also produces its major inactive metabolite, phenylcyclohexylglycolic acid.
In multiple, large clinical trials of oxybutynin therapy for overactive bladder syndrome, serum enzyme elevations were rare and no more frequent than with placebo, and there were no episodes of clinically apparent liver injury. Since its approval and widespread use for more than four decades, there has been only a single published case of suspected liver injury attributed to oxybutynin – a report of transient serum enzyme elevations without jaundice or apparent symptoms in a patient with a severe ischemic stroke arising within weeks of starting oxybutynin. Thus, clinically apparent liver injury from oxybutynin is very rare if it occurs at all.
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：根据药物导致人类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
Oxybutynin should be swallowed whole with the help of liquids. A pharmacokinetic study revealed that oxybutynin was rapidly absorbed, and peak concentrations were reached within about 1 hour of administration, measured at 8.2 ngml-1 and AUC was 16 ngml-1. The biovailability of oxybutynin is about 6%, and the plasma concentration of the active metabolite, desethyloxybutynin is 5 to 12 times greater than that of oxybutynin. Bioavailability is increased in the elderly. Food has been shown to increase the exposure to controlled-release oxybutynin.
Oxybutynin is heavily cleared by the liver. Under 0.1% of an administered dose is found as unchanged drug in the urine. Less than 0.1% of a single dose of oxybutynin is excreted as desethyloxybutynin.
Material Safety Data Sheet Section 1. Identification of the substance Product Name: Oxybutynin Synonyms: Section 2. Hazards identification Harmful by inhalation, in contact with skin, and if swallowed. Section 3. Composition/information on ingredients. Ingredient name: Oxybutynin CAS number: 5633-20-5 Section 4. First aid measures Skin contact: Immediately wash skin with copious amounts of water for at least 15 minutes while removing contaminated clothing and shoes. If irritation persists, seek medical attention. Eye contact: Immediately wash skin with copious amounts of water for at least 15 minutes. Assure adequate flushing of the eyes by separating the eyelids with fingers. If irritation persists, seek medical attention. Inhalation: Remove to fresh air. In severe cases or if symptoms persist, seek medical attention. Ingestion: Wash out mouth with copious amounts of water for at least 15 minutes. Seek medical attention. Section 5. Fire fighting measures In the event of a fire involving this material, alone or in combination with other materials, use dry powder or carbon dioxide extinguishers. Protective clothing and self-contained breathing apparatus should be worn. Section 6. Accidental release measures Personal precautions: Wear suitable personal protective equipment which performs satisfactorily and meets local/state/national standards. Respiratory precaution: Wear approved mask/respirator Hand precaution: Wear suitable gloves/gauntlets Skin protection: Wear suitable protective clothing Eye protection: Wear suitable eye protection Methods for cleaning up: Mix with sand or similar inert absorbent material, sweep up and keep in a tightly closed container for disposal. See section 12. Environmental precautions: Do not allow material to enter drains or water courses. Section 7. Handling and storage Handling: This product should be handled only by, or under the close supervision of, those properly qualified in the handling and use of potentially hazardous chemicals, who should take into account the fire, health and chemical hazard data given on this sheet. Store in closed vessels, refrigerated. Storage: Section 8. Exposure Controls / Personal protection Engineering Controls: Use only in a chemical fume hood. Personal protective equipment: Wear laboratory clothing, chemical-resistant gloves and safety goggles. General hydiene measures: Wash thoroughly after handling. Wash contaminated clothing before reuse. Section 9. Physical and chemical properties Appearance: Not specified Boiling point: No data No data Melting point: Flash point: No data Density: No data Molecular formula: C22H31NO3 Molecular weight: 357.5 Section 10. Stability and reactivity Conditions to avoid: Heat, flames and sparks. Materials to avoid: Oxidizing agents. Possible hazardous combustion products: Carbon monoxide, nitrogen oxides. Section 11. Toxicological information No data. Section 12. Ecological information No data. Section 13. Disposal consideration Arrange disposal as special waste, by licensed disposal company, in consultation with local waste disposal authority, in accordance with national and regional regulations. Section 14. Transportation information Non-harzardous for air and ground transportation. Section 15. Regulatory information No chemicals in this material are subject to the reporting requirements of SARA Title III, Section 302, or have known CAS numbers that exceed the threshold reporting levels established by SARA Title III, Section 313.
[EN] COMPOUNDS AND THEIR USE AS BACE INHIBITORS<br/>[FR] COMPOSÉS ET LEUR UTILISATION EN TANT QU'INHIBITEURS DE BACE
申请人：ASTRAZENECA AB
公开号：WO2016055858A1
公开（公告）日：2016-04-14
The present application relates to compounds of formula (I), (la), or (lb) and their pharmaceutical compositions/preparations. This application further relates to methods of treating or preventing Αβ-related pathologies such as Down's syndrome, β- amyloid angiopathy such as but not limited to cerebral amyloid angiopathy or hereditary cerebral hemorrhage, disorders associated with cognitive impairment such as but not limited to MCI ("mild cognitive impairment"), Alzheimer's disease, memory loss, attention deficit symptoms associated with Alzheimer's disease, neurodegeneration associated with diseases such as Alzheimer's disease or dementia, including dementia of mixed vascular and degenerative origin, pre-senile dementia, senile dementia and dementia associated with Parkinson's disease.
[EN] N-PYRAZOLYL CARBOXAMIDES AS CRAC CHANNEL INHIBITORS<br/>[FR] CARBOXAMIDES N-PYRAZOLYL EN TANT QU'INHIBITEURS DU CANAL CRAC
申请人：GLAXO GROUP LTD
公开号：WO2010122089A1
公开（公告）日：2010-10-28
The present invention relates to amide compounds, processes for their preparation, pharmaceutical compositions containing these compounds and to their use in the treatment of disorders, conditions or disorders such as allergic disorders, inflammatory disorders and disorders of the immune system.
[EN] ISOTOPE ENHANCED AMBROXOL FOR LONG LASTING AUTOPHAGY INDUCTION<br/>[FR] AMBROXOL À ISOTOPE AMÉLIORÉ POUR INDUCTION D'AUTOPHAGIE DURABLE
申请人：STC UNM
公开号：WO2018148113A1
公开（公告）日：2018-08-16
The present invention is directed to 13C and/or 2H isotope enhanced ambroxol ("isotope enhanced ambroxol") and its use in the treatment of autophagy infections, especially mycobacterial and other infections, disease states and/or conditions of the lung, such as tuberculosis, especially including drug resistant and multiple drag resistant tuberculosis. Pharmaceutical compositions comprising isotope enhanced amhroxol, alone or in combination with an additional bioactive agent, especially rifamycin antibiotics, including an additional autophagy modulator (an agent which is active to promote or inhibit autophagy), thus being useful against, an autophagy mediated disease state and/or condition), especially an antophagy mediated disease state and/or condition which occurs in the lungs, for example, a Mycobacterium infection. Chronic Obstructive Pulmonary Disease (COPD), asthma, pulmonary fibrosis, cystic fibrosis, Sjogren's disease and lung cancer (small cell and non-small cell lung cancer, among other disease states and/or conditions, especially of the lung. Methods of treating autophagy disease states and/or conditions, especially including autophagy disease states or conditions which occur principally in the lungs of a patient represent a further embodiment of the present invention. An additional embodiment includes methods of synthesizing compounds according to the present invention as otherwise disclosed herein.
[EN] 3,6-DISUBSTITUTED AZABICYCLO [3.1.0] HEXANE DERIVATIVES AS MUSCARINIC RECEPTOR ANTAGONISTS<br/>[FR] DERIVES D'AZABICYCLO [3.1.0] HEXANE 3,6-DISUBSTITUES UTILISES COMME ANTAGONISTES DU RECEPTEUR MUSCARINIQUE
申请人：RANBAXY LAB LTD
公开号：WO2004052857A1
公开（公告）日：2004-06-24
The invention relates to derivatives of 3,6-disubstituted azabicyclo [3.1.0] hexanes of structure (I). The compounds of this invention can function as muscarinic receptor antagonists, and can be used for the treatment of various diseases of the respiratory, urinary and gastrointestinal systems mediated through muscarinic receptors. The invention also relates to pharmaceutical compositions containing the compounds of the present invention and the methods for treating the diseases mediated through muscarinic receptors.
[EN] SUBSTITUTED AZABICYCLO HEXANE DERIVATIVES AS MUSCARINIC RECEPTOR ANTAGONISTS<br/>[FR] DERIVES D'AZABICYCLO HEXANES SUBSTITUES EN TANT QU'ANTAGONISTES DES RECEPTEURS MUSCARINIQUES
申请人：RANBAXY LAB LTD
公开号：WO2004089363A1
公开（公告）日：2004-10-21
This invention generally relates to derivatives of substituted azabicyclo hexanes of formula I. The compounds of this invention can function as muscarinic receptor antagonists, and can be used for the treatment of various diseases of the respiratory, urinary and gastrointestinal systems mediated through muscarinic receptors. The invention also relates to a process for the preparation of the compounds of the present invention, pharmaceutical compositions containing the compounds of the present invention and the methods of treating the diseases mediated through muscarinic receptors.
