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药品详细

Atomoxetine(托莫西汀)

化学结构式图
中文名
托莫西汀
英文名
Atomoxetine
分子式
C17H21NO
化学名
methyl[(3R)-3-(2-methylphenoxy)-3-phenylpropyl]amine
分子量
Average: 255.3547
Monoisotopic: 255.162314299
CAS号
82248-59-7
ATC分类
N06B 未知
药物类型
small molecule
阶段
approved
商品名
同义名
基本介绍

Atomoxetine is the first non-stimulant drug approved for the treatment of attention-deficit hyperactivity disorder (ADHD). It is sold in the form of the hydrochloride salt of atomoxetine. This chemical is manufactured and marketed under the brand name Strattera; by Eli Lilly and Company and as a generic Attentin by Torrent Pharmaceuticals. There is currently no generic available within the United States due to patent restrictions. [Wikipedia]

生产厂家
  • Eli lilly and co
封装厂家
参考
Synthesis Reference Not Available
General Reference
  1. Spencer TJ, Faraone SV, Michelson D, Adler LA, Reimherr FW, Glatt SJ, Biederman J: Atomoxetine and adult attention-deficit/hyperactivity disorder: the effects of comorbidity. J Clin Psychiatry. 2006 Mar;67(3):415-20. Pubmed
  2. Pilhatsch MK, Burghardt R, Wandinger KP, Bauer M, Adli M: Augmentation with atomoxetine in treatment-resistant depression with psychotic features. A case report. Pharmacopsychiatry. 2006 Mar;39(2):79-80. Pubmed
  3. Carpenter LL, Milosavljevic N, Schecter JM, Tyrka AR, Price LH: Augmentation with open-label atomoxetine for partial or nonresponse to antidepressants. J Clin Psychiatry. 2005 Oct;66(10):1234-8. Pubmed
  4. Kratochvil CJ, Newcorn JH, Arnold LE, Duesenberg D, Emslie GJ, Quintana H, Sarkis EH, Wagner KD, Gao H, Michelson D, Biederman J: Atomoxetine alone or combined with fluoxetine for treating ADHD with comorbid depressive or anxiety symptoms. J Am Acad Child Adolesc Psychiatry. 2005 Sep;44(9):915-24. Pubmed
  5. McElroy SL, Guerdjikova A, Kotwal R, Welge JA, Nelson EB, Lake KA, Keck PE Jr, Hudson JI: Atomoxetine in the treatment of binge-eating disorder: a randomized placebo-controlled trial. J Clin Psychiatry. 2007 Mar;68(3):390-8. Pubmed
  6. Purper-Ouakil D, Fourneret P, Wohl M, Reneric JP: [Atomoxetine: a new treatment for Attention Deficit/Hyperactivity Disorder (ADHD) in children and adolescents] Encephale. 2005 May-Jun;31(3):337-48. Pubmed# Simpson D, Plosker GL: Atomoxetine: a review of its use in adults with attention deficit hyperactivity disorder. Drugs. 2004;64(2):205-22. Pubmed
  7. Montoya A, Hervas A, Cardo E, Artigas J, Mardomingo MJ, Alda JA, Gastaminza X, Garcia-Polavieja MJ, Gilaberte I, Escobar R: Evaluation of atomoxetine for first-line treatment of newly diagnosed, treatment-naive children and adolescents with attention deficit/hyperactivity disorder. Curr Med Res Opin. 2009 Nov;25(11):2745-54. Pubmed
  8. Gaillez C, Sorbara F, Perrin E: [Atomoxetine (Strattera), an alternative in the treatment of attention-deficit/hyperactivity disorder (ADHD) in children] Encephale. 2007 Sep;33(4 Pt 1):621-8. Pubmed
剂型
规格
化合物类型
Type small molecule
Classes
  • Phenylpropylamines
Substructures
  • Benzyl Alcohols and Derivatives
  • Aliphatic and Aryl Amines
  • Phenols and Derivatives
  • Ethers
  • Benzene and Derivatives
  • Aromatic compounds
  • Anisoles
  • Phenylpropylamines
  • Phenyl Esters
适应症
药理
Indication For the treatment of Attention-Deficit/Hyperactivity Disorder (ADHD) alone or in combination with behavioral treatment, as an adjunct to psychological, educational, social, and other remedial measures.
Pharmacodynamics Atomoxetine is the first non-stimulant drug approved for the treatment of attention-deficit hyperactivity disorder (ADHD). Atomoxetine is classified as a norepinephrine reuptake inhibitor, and is approved for use in children, adolescents, and adults. However, its efficacy has not been studied in children under six years old. Its advantage over stimulants for the treatment of ADHD is that it has less abuse potential than stimulants, is not scheduled as a controlled substance and has proven in clinical trials to offer 24 hour coverage of symptoms associated with ADHD in adults and children.
Mechanism of action The precise mechanism by which atomoxetine produces its therapeutic effects in Attention-Deficit/Hyperactivity Disorder (ADHD) is unknown, but is thought to be related to selective inhibition of the pre-synaptic norepinephrine transporter, as determined through in-vitro studies. Atomoxetine appears to have minimal affinity for other noradrenergic receptors or for other neurotransmitter transporters or receptors.
Absorption Atomoxetine is rapidly absorbed after oral administration, with absolute bioavailability of about 63% in EMs and 94% in PMs. Drugs that elevate gastric pH (magnesium hydroxide/aluminum hydroxide, omeprazole) have no effect on atomoxetine bioavailability. Absorption is minimally affected by food.
Volume of distribution
  • 0.85 L/kg
Protein binding At therapeutic concentrations, 98% of atomoxetine in plasma is bound to protein, primarily albumin.
Metabolism
Atomoxetine is primarily metabolized by the CYP2D6 pathway to 4-hydroxyatomoxetine. 4-Hydroxyatomoxetine is equipotent to atomoxetine as an inhibitor of the norepinephrine transporter but circulates in plasma at much lower concentrations (1% of atomoxetine concentration in EMs and 0.1% of atomoxetine concentration in PMs).

Important The metabolism module of DrugBank is currently in beta. Questions or suggestions? Please contact us.

Substrate Enzymes Product
Atomoxetine
    		4-hydroxyatomoxetine Details
    Route of elimination Not Available
    Half life 5 hours
    Clearance
    • 0.35 L/hr/kg [after oral administration in adult extensive metabolizers]
    • 0.03 L/hr/kg [administration of atomoxetine to poor metabolizers]
    Toxicity The most commonly reported symptoms accompanying acute and chronic overdoses are somnolence, agitation, hyperactivity, abnormal behavior, and gastrointestinal symptoms.
    Affected organisms
    • Humans and other mammals
    Pathways Not Available
    理化性质
    Properties
    State solid
    Experimental Properties
    Property Value Source
    water solubility 27.8 mg/mL Not Available
    logP 3.9 Not Available
    Predicted Properties
    Property Value Source
    water solubility 3.90e-03 g/l ALOGPS
    logP 3.95 ALOGPS
    logP 3.81 ChemAxon
    logS -4.8 ALOGPS
    pKa (strongest basic) 9.8 ChemAxon
    physiological charge 1 ChemAxon
    hydrogen acceptor count 2 ChemAxon
    hydrogen donor count 1 ChemAxon
    polar surface area 21.26 ChemAxon
    rotatable bond count 6 ChemAxon
    refractivity 79.44 ChemAxon
    polarizability 29.79 ChemAxon
    药物相互作用
    Drug Interaction
    Amiodarone The CYP2D6 inhibitor could increase the effect and toxicity of atomoxetine
    Chloroquine The CYP2D6 inhibitor could increase the effect and toxicity of atomoxetine
    Cocaine CYP2D6 Inhibitors (Strong) such as cocaine may increase the serum concentration of atomoxetine. Initiate atomoxetine at a reduced dose (patients up to 70kg: 0.5mg/kg/day; patients 70kg or more: 40mg/day) in patients receiving a strong CYP2D6 inhibitor. The dose should only be increased to usual doses if symptoms fail to improve after 4 weeks. Patients established on atomoxetine therapy may require dosage reductions and should be monitored for increased levels/adverse effects with initiation/dose increase of a strong CYP2D6 inhibitor.
    Diphenhydramine Diphenhydramine, a moderate CYP2D6 inhibitor, may increase the therapeutic and adverse effects of atomoxetine by decreasing its metabolism.
    Fluoxetine The CYP2D6 inhibitor could increase the effect and toxicity of atomoxetine
    Fluphenazine Risk of additive CNS depressant effects. Monitor for increased CNS depression during concomitant therapy.
    Haloperidol The CYP2D6 inhibitor could increase the effect and toxicity of atomoxetine
    Isocarboxazid Possible severe adverse reaction with this combination
    Lomustine The CYP2D6 inhibitor could increase the effect and toxicity of atomoxetine
    Mibefradil The CYP2D6 inhibitor could increase the effect and toxicity of atomoxetine
    Paroxetine The CYP2D6 inhibitor, paroxetine, may increase the effect and toxicity of atomoxetine.
    Perphenazine The CYP2D6 inhibitor could increase the effect and toxicity of atomoxetine
    Phenelzine Possible severe adverse reaction with this combination
    Propoxyphene The CYP2D6 inhibitor could increase the effect and toxicity of atomoxetine
    Quinacrine The CYP2D6 inhibitor could increase the effect and toxicity of atomoxetine
    Quinidine The CYP2D6 inhibitor could increase the effect and toxicity of atomoxetine
    Quinidine barbiturate The CYP2D6 inhibitor could increase the effect and toxicity of atomoxetine
    Quinine The CYP2D6 inhibitor could increase the effect and toxicity of atomoxetine
    Rasagiline Possible severe adverse reaction with this combination
    Ritonavir The CYP2D6 inhibitor could increase the effect and toxicity of atomoxetine
    Terbinafine Terbinafine, a CYP2D6 inhibitor, may reduce the metabolism and clearance of Atomoxetine. Consider alternate therapy or monitor for therapeutic/adverse effects of Atomoxetine if Terbinafine is initiated, discontinued or dose changed.
    Thioridazine The CYP2D6 inhibitor could increase the effect and toxicity of atomoxetine
    Tranylcypromine The MAO inhibitor, Tranylcypromine, may increase the central neurotoxic effects of the Atomoxetine. These agents should not be administered within 14 days of each other.
    Triprolidine The CNS depressants, Triprolidine and Atomoxetine, may increase adverse/toxic effects due to additivity. Monitor for increased CNS depressant effects during concomitant therapy.
    Vinorelbine The CYP2D6 inhibitor could increase the effect and toxicity of atomoxetine
    Yohimbine The CYP2D6 inhibitor could increase the effect and toxicity of atomoxetine
    食物相互作用
    • In the presence of food, the absorption rate is reduced, without the quantity absorbed being affected.
    • Take without regard to meals.

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