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药品详细

Tapentadol(他喷他多)

化学结构式图
中文名
他喷他多
英文名
Tapentadol
分子式
C14H23NO
化学名
3-[(2R,3R)-1-(dimethylamino)-2-methylpentan-3-yl]phenol
分子量
Average: 221.3385
Monoisotopic: 221.177964363
CAS号
175591-23-8
ATC分类
N02A 未知
药物类型
small molecule
阶段
approved
商品名
同义名
基本介绍

Opioid analgesic for treatment of moderate to severe pain. FDA approved on Nov 20, 2008.

生产厂家
  • Ortho mcneil janssen pharmaceuticals inc
封装厂家
参考
Synthesis Reference Not Available
General Reference
  1. Tzschentke TM, Christoph T, Kogel B, Schiene K, Hennies HH, Englberger W, Haurand M, Jahnel U, Cremers TI, Friderichs E, De Vry J: (-)-(1R,2R)-3-(3-dimethylamino-1-ethyl-2-methyl-propyl)-phenol hydrochloride (tapentadol HCl): a novel mu-opioid receptor agonist/norepinephrine reuptake inhibitor with broad-spectrum analgesic properties. J Pharmacol Exp Ther. 2007 Oct;323(1):265-76. Epub 2007 Jul 26. Pubmed
  2. Gohler K, Brett M, Smit JW, Rengelshausen J, Terlinden R: Comparative pharmacokinetics and bioavailability of tapentadol following oral administration of immediate- and prolonged-release formulations. Int J Clin Pharmacol Ther. 2013 Apr;51(4):338-48. doi: 10.5414/CP201722. Pubmed
  3. Xu XS, Smit JW, Lin R, Stuyckens K, Terlinden R, Nandy P: Population pharmacokinetics of tapentadol immediate release (IR) in healthy subjects and patients with moderate or severe pain. Clin Pharmacokinet. 2010 Oct;49(10):671-82. doi: 10.2165/11535390-000000000-00000. 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 The immediate-release formulation of tapentadol is indicated for the relief of moderate to severe acute pain. The long-acting formulation serves as a continuous, around-the-clock analgesic that is indicated for the relief of moderate to severe chronic pain or neuropathic pain associated with diabetic peripheral neuropathy.
Pharmacodynamics Tapentadol is a centrally-acting synthetic analgesic. It is 18 times less potent than morphine in terms of binding to human mu-opioid receptors. It also increases norepinephrine concentrations in the brains of rats via inhibition of norepinephrine reuptake. Selective mu-opioid antagonists like naloxone can block analgesia from tapentadol. It also has not effect on the QT interval.
Mechanism of action Tapendadol causes large increases in levels of extracellular norepinephrine (NE) due to a dual mechanism of action involving mu opioid receptor (MOR) agonism as well as noradrenaline reuptake inhibition.
Absorption Bioavailability, immediate release (IR), 86 mg: 32%; Bioavailability, extended release (ER), 86 mg: 32%; Cmax, IR: 64.2 ng/mL; Cmax, ER: 22.5 ng/mL; T max, IR: 1.5 hours; T max, ER: 5.0 hours; Tapentadol accumulates following multiple repeat doses.
Volume of distribution

Following IV administration, volume of distribution is 540 ± 98 L.
Protein binding ~20%
Metabolism
97% of the dose is metabolized mostly via conjugation with glucuronic acid to produce glucuronides. Tapentadol is also metabolized into N-desmethyl tapentadol (13%) by CYP2C9 and CYP 2C19. CYP2D6 is involved in the formation of the metabolite, hydroxy tapentadol (2%). All metabolites are inactive.

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

Substrate Enzymes Product
Tapentadol
    		N-desmethyl tapentadol Details
    Route of elimination Tapentadol and its metabolites are excreted almost exclusively (99%) via the kidneys. Approximately 70% (55% O-glucuronide and 15% sulfate of tapentadol) is excreted in conjugated form. A total of 3% of drug was excreted in urine as unchanged drug.
    Half life Elimination half-life, IV: 4 hours.
    Clearance

    Total clearance = 1530 ± 177 ml/min.
    Toxicity Oral, rabbit: LD50 = 3200 mg/kg; Oral, mouse: LD50 = 300 mg/kg; Oral, rat: LD50: 980 mg/kg; The most common reasons for discontinuation due to adverse events were dizziness, nausea, vomiting, somnolence, and headache.
    Affected organisms
    • Humans and other mammals
    Pathways Not Available
    理化性质
    Properties
    State solid
    Experimental Properties
    Property Value Source
    logP 2.87 FDA label
    pKa 9.34 - 10.45 FDA label
    Predicted Properties
    Property Value Source
    water solubility 7.80e-01 g/l ALOGPS
    logP 3.47 ALOGPS
    logP 2.96 ChemAxon
    logS -2.5 ALOGPS
    pKa (strongest acidic) 10.28 ChemAxon
    pKa (strongest basic) 9.6 ChemAxon
    physiological charge 1 ChemAxon
    hydrogen acceptor count 2 ChemAxon
    hydrogen donor count 1 ChemAxon
    polar surface area 23.47 ChemAxon
    rotatable bond count 5 ChemAxon
    refractivity 69.56 ChemAxon
    polarizability 26.58 ChemAxon
    药物相互作用
    Drug Interaction
    Alvimopan Increases levels by receptor binding competition. Discontinue opioid administration at least 7 days prior to administrating Alvimopan.
    Desvenlafaxine Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
    Naproxen Increases the AUC of tapentadol by 17%. These changes are not considered clinically relevant and no change in dose is required.
    Probenecid Increases the AUC of tapentadol by 57%. These changes are not considered clinically relevant and no change in dose is required.
    Rasagiline Increases the toxicity of tapentadol by unknown mechanism. Discontinue rasagiline at least 14 days prior to tapentadol administration.
    Selegiline Increases the toxicity of tapentadol by unknown mechanism. Discontinue selegiline at least 14 days prior to tapentadol administration.
    Zolmitriptan Use of two serotonin modulators, such as zolmitriptan and tapentadol, increases the risk of serotonin syndrome. Consider alternate therapy or monitor for serotonin syndrome during concomitant therapy.
    食物相互作用
    • Food increases the AUC and Cmax of tapentadol. Despite this, tapentadol can be given without regards to food.

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