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药品详细

Aclidinium(阿地)

化学结构式图
中文名
阿地
英文名
Aclidinium
分子式
C26H30BrNO4S2
化学名
3-{[2-hydroxy-2,2-bis(thiophen-2-yl)acetyl]oxy}-1-(3-phenoxypropyl)-1-azabicyclo[2.2.2]octan-1-ium bromide
分子量
Average: 564.555
Monoisotopic: 563.07996248
CAS号
320345-99-1
ATC分类
R03B 未知
药物类型
small molecule
阶段
approved
商品名
同义名
基本介绍

Aclidinium is an anticholinergic for the long-term management of chronic obstructive pulmonary disease (COPD). It has a much higher propensity to bind to muscarinic receptors than nicotinic receptors. FDA approved on July 24, 2012.

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    参考
    Synthesis Reference Not Available
    General Reference
    1. FDA label
    2. Reid DJ, Pham NT: Emerging Therapeutic Options for the Management of COPD. Clin Med Insights Circ Respir Pulm Med. 2013 Apr 9;7:7-15. doi: 10.4137/CCRPM.S8140. Print 2013. Pubmed
    3. Cazzola M, Page CP, Matera MG: Aclidinium bromide for the treatment of chronic obstructive pulmonary disease. Expert Opin Pharmacother. 2013 Jun;14(9):1205-14. doi: 10.1517/14656566.2013.789021. Epub 2013 Apr 9. Pubmed
    4. Jones P: Aclidinium bromide twice daily for the treatment of chronic obstructive pulmonary disease: a review. Adv Ther. 2013 Apr;30(4):354-68. doi: 10.1007/s12325-013-0019-2. Epub 2013 Apr 2. Pubmed
    剂型
    规格
    化合物类型
    Type small molecule
    Classes Not Available
    Substructures Not Available
    适应症
    药理
    Indication Aclidinium bromide inhalation powder is indicated for the long-term, maintenance treatment of bronchospasm associated with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and emphysema.
    Pharmacodynamics Aclidinium does not prolong the QTc interval or have significant effects on cardiac rhythm.
    Mechanism of action Aclidinium is a long-acting, competitive, and reversible anticholinergic drug that is specific for the acetylcholine muscarinic receptors. It binds to all 5 muscarinic receptor subtypes to a similar affinity. Aclidinium's effects on the airways are mediated through the M3 receptor at the smooth muscle to cause bronchodilation. Prevention of acetylcholine-induced bronchoconstriction effects was dose-dependent and lasted longer than 24 hours.
    Absorption Bioavailability, healthy subjects = 6%; T max, healthy subjects = 10 minutes; Time to steady state, healthy subjects = 2 days;
    Volume of distribution

    Following IV administration, the volume of distribution is 300 L
    Protein binding Not Available
    Metabolism
    The major route of metabolism of aclidinium bromide is hydrolysis, which occurs both chemically and enzymatically by esterases in the plasma. Aclidinium bromide is rapidly and extensively hydrolyzed to its alcohol and dithienylglycolic acid derivatives, neither of which binds to muscarinic receptors and are pharmacologically inactive.
    Route of elimination Intravenously administered radiolabelled aclidinium bromide was administered to healthy volunteers and was extensively metabolized with 1% excreted as unchanged aclidinium. Approximately 54% to 65% of the radioactivity was excreted in urine and 20% to 33% of the dose was excreted in feces. The combined results indicated that almost the entire aclidinium bromide dose was eliminated by hydrolysis. After dry powder inhalation, urinary excretion of aclidinium is about 0.09% of the dose.
    Half life Plasma half-life = 2.4 minutes (indicating that aclidinium is very rapidly hydrolyzed in plasma into its two inactive metabolites and has a low chance of causing systemic side effects). Effective half-life = 5-8 hours.
    Clearance

    Total clearance, IV dose, young healthy subjects = 170 L/h (inter-individual variability of 36%)
    Toxicity Most common adverse reactions (≥3% incidence and greater than placebo) are headache, nasopharyngitis and cough.
    Affected organisms
    • Humans and other mammals
    Pathways Not Available
    理化性质
    Properties
    State solid
    Experimental Properties
    Property Value Source
    water solubility Very slightly soluble FDA label
    Predicted Properties
    Property Value Source
    water solubility 1.90e-03 g/l ALOGPS
    logP 2.24 ALOGPS
    logP 0.45 ChemAxon
    logS -5.5 ALOGPS
    pKa (strongest acidic) 10.35 ChemAxon
    pKa (strongest basic) -4.8 ChemAxon
    physiological charge 1 ChemAxon
    hydrogen acceptor count 3 ChemAxon
    hydrogen donor count 1 ChemAxon
    polar surface area 55.76 ChemAxon
    rotatable bond count 10 ChemAxon
    refractivity 141.33 ChemAxon
    polarizability 52.16 ChemAxon
    药物相互作用
    Drug Interaction
    Pramlintide May increase the risk of inhibition of GI motility via pharmacodynamic synergism. Consider alternate therapy.
    食物相互作用
    Not Available

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