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药品详细

Theophylline(茶碱)

化学结构式图
中文名
茶碱
英文名
Theophylline
分子式
C7H8N4O2
化学名
1,3-dimethyl-2,3,6,7-tetrahydro-1H-purine-2,6-dione
分子量
Average: 180.164
Monoisotopic: 180.06472552
CAS号
58-55-9
ATC分类
R03D 未知;R03D 未知
药物类型
small molecule
阶段
approved
商品名
同义名
基本介绍

A methylxanthine derivative from tea with diuretic, smooth muscle relaxant, bronchial dilation, cardiac and central nervous system stimulant activities. Mechanistically, theophylline acts as a phosphodiesterase inhibitor, adenosine receptor blocker, and histone deacetylase activator. Theophylline is marketed under several brand names such as Uniphyl and Theochron, and it is indicated mainly for asthma, bronchospasm, and COPD.

生产厂家
  • 3m pharmaceuticals inc
  • Able laboratories inc
  • Alpharma us pharmaceuticals division
  • B braun medical inc
  • Baxter healthcare corp
  • Caraco pharmaceutical laboratories ltd
  • Cenci powder products inc
  • Central pharmaceuticals inc
  • Dm graham laboratories inc
  • Ferndale laboratories inc
  • Fisons corp
  • Fleming and co pharmaceuticals inc
  • Forest laboratories inc
  • Glenmark generics ltd
  • Graceway pharmaceuticals llc
  • Halsey drug co inc
  • Hospira inc
  • Hr cenci laboratories inc
  • Inwood laboratories inc sub forest laboratories inc
  • Kv pharmaceutical co
  • L perrigo co
  • Lannett co inc
  • Monarch pharmaceuticals inc
  • Nostrum pharmaceuticals inc
  • Novartis consumer health inc
  • Ortho mcneil pharmaceutical inc
  • Panray corp sub ormont drug and chemical co inc
  • Pharmaceutical assoc inc div beach products
  • Pharmaceutical research assoc inc
  • Pliva inc
  • Precision dose inc
  • Purdue pharmaceutical products lp
  • Roerig div pfizer inc
  • Roxane laboratories inc
  • Rp scherer north america
  • Rp scherer north america div rp scherer corp
  • Sandoz inc
  • Sanofi aventis us llc
  • Schering corp
  • Schering corp sub schering plough corp
  • Schwarz pharma inc
  • Taro pharmaceuticals usa inc
  • Ucb inc
  • Warner chilcott co llc
  • Whitby pharmaceuticals inc
  • Wockhardt eu operations (swiss) ag
封装厂家
参考
Synthesis Reference Not Available
General Reference Not Available
剂型
规格
化合物类型
Type small molecule
Classes
  • Xanthines
Substructures
  • Xanthines
  • Pyrimidines and Derivatives
  • Imidazoles
  • Heterocyclic compounds
  • Aromatic compounds
  • Purines and Purine Derivatives
  • Cyanamides
适应症
药理
Indication For the treatment of the symptoms and reversible airflow obstruction associated with chronic asthma and other chronic lung diseases, such as emphysema and chronic bronchitis.
Pharmacodynamics Theophylline, an xanthine derivative chemically similar to caffeine and theobromine, is used to treat asthma and bronchospasm. Theophylline has two distinct actions in the airways of patients with reversible (asthmatic) obstruction; smooth muscle relaxation (i.e., bronchodilation) and suppression of the response of the airways to stimuli (i.e., non-bronchodilator prophylactic effects).
Mechanism of action Theophylline relaxes the smooth muscle of the bronchial airways and pulmonary blood vessels and reduces airway responsiveness to histamine, methacholine, adenosine, and allergen. Theophylline competitively inhibits type III and type IV phosphodiesterase (PDE), the enzyme responsible for breaking down cyclic AMP in smooth muscle cells, possibly resulting in bronchodilation. Theophylline also binds to the adenosine A2B receptor and blocks adenosine mediated bronchoconstriction. In inflammatory states, theophylline activates histone deacetylase to prevent transcription of inflammatory genes that require the acetylation of histones for transcription to begin.
Absorption Theophylline is rapidly and completely absorbed after oral administration in solution or immediate-release solid oral dosage form.
Volume of distribution
  • 0.3 to 0.7 L/kg
Protein binding 40%, primarily to albumin.
Metabolism
Hepatic. Biotransformation takes place through demethylation to 1-methylxanthine and 3-methylxanthine and hydroxylation to 1,3-dimethyluric acid. 1-methylxanthine is further hydroxylated, by xanthine oxidase, to 1-methyluric acid. About 6% of a theophylline dose is N-methylated to caffeine. Caffeine and 3-methylxanthine are the only theophylline metabolites with pharmacologic activity.

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

Substrate Enzymes Product
Theophylline
1-methylxanthine Details
Theophylline
3-methylxanthine Details
Theophylline
1,3-dimethyluric acid Details
Theophylline
    		Caffeine Details
    Route of elimination Theophylline does not undergo any appreciable pre-systemic elimination, distributes freely into fat-free tissues and is extensively metabolized in the liver. Renal excretion of unchanged theophylline in neonates amounts to about 50% of the dose, compared to about 10% in children older than three months and in adults.
    Half life 8 hours
    Clearance
    • 0.29 mL/kg/min [Premature neonates, postnatal age 3-15 days]
    • 0.64 mL/kg/min [Premature neonates, postnatal age 25-57 days]
    • 1.7 mL/kg/min [Children 1-4 years]
    • 1.6 mL/kg/min [Children 4-12 years]
    • 0.9 mL/kg/min [Children 13-15 years]
    • 1.4 mL/kg/min [Children 16-17 years]
    • 0.65 mL/kg/min [Adults (16-60 years), otherwise healthy non-smoking asthmatics]
    • 0.41 mL/kg/min [Elderly (>60 years), non-smokers with normal cardiac, liver, and renal function]
    • 0.33 mL/kg/min [Acute pulmonary edema]
    • 0.54 mL/kg/min [COPD >60 years, stable, non-smoker >1 year]
    • 0.48 mL/kg/min [COPD with cor pulmonale]
    • 1.25 mL/kg/min [Cystic fibrosis (14-28 years)]
    • 0.31 mL/kg/min [Liver disease cirrhosis]
    • 0.35 mL/kg/min [acute hepatitis]
    • 0.65 mL/kg/min [cholestasis]
    • 0.47 mL/kg/min [Sepsis with multi-organ failure]
    • 0.38 mL/kg/min [hypothyroid]
    • 0.8 mL/kg/min [hyperthyroid]
    Toxicity Symptoms of overdose include seizures, arrhythmias, and GI effects.
    Affected organisms
    • Humans and other mammals
    Pathways Not Available
    理化性质
    Properties
    State solid
    Experimental Properties
    Property Value Source
    melting point 273 °C PhysProp
    water solubility 7360 mg/L (at 25 °C) YALKOWSKY,SH & HE,Y (2003)
    logP -0.02 HANSCH,C ET AL. (1995)
    Caco2 permeability -4.35 ADME Research, USCD
    pKa 8.81 KORTUM,G ET AL (1961)
    Predicted Properties
    Property Value Source
    water solubility 2.29e+01 g/l ALOGPS
    logP -0.26 ALOGPS
    logP -0.77 ChemAxon
    logS -0.9 ALOGPS
    pKa (strongest acidic) 7.82 ChemAxon
    pKa (strongest basic) -0.78 ChemAxon
    physiological charge 0 ChemAxon
    hydrogen acceptor count 3 ChemAxon
    hydrogen donor count 1 ChemAxon
    polar surface area 69.3 ChemAxon
    rotatable bond count 0 ChemAxon
    refractivity 44.93 ChemAxon
    polarizability 16.86 ChemAxon
    药物相互作用
    Drug Interaction
    Acyclovir Acyclovir may increase the effect and toxicity of theophylline.
    Adenosine Theophylline may decrease the effect of adenosine.
    Amobarbital The barbiturate, amobarbital, decreases the effect of theophylline.
    Aprobarbital The barbiturate, aprobarbital, decreases the effect of theophylline.
    Atracurium Theophylline decreases the effect of the muscle relaxant
    Bromazepam Theophylline may decrease the therapeutic effect of bromazepam. Monitor for changes in the therapeutic effects of bromazepam if theophylline is initiated, discontinued or dose changed.
    Butabarbital The barbiturate, butabarbital, decreases the effect of theophylline.
    Butalbital The barbiturate, butalbital, decreases the effect of theophylline.
    Butethal The barbiturate, butethal, decreases the effect of theophylline.
    Carbamazepine Carbamazepine may decrease the serum concentration of theophylline. Theophylline may decrease the serum concentration of carbamazepine. Monitor for changes in the therapeutic effect of both agents if concomitant therapy is initiated, discontinued or dose changed.
    Carteolol Antagonism of action and increased effect of theophylline
    Cimetidine Cimetidine may increase the effect of theophylline.
    Ciprofloxacin Ciprofloxacin may increase the effect of theophylline.
    Clarithromycin Clarithromycin may increase the therapeutic and adverse effects of theophylline.
    Dihydroquinidine barbiturate The barbiturate, dihydroquinidine barbiturate, decreases the effect of theophylline.
    Disulfiram Disulfiram may increase the effect and toxicity of theophylline.
    Doxacurium chloride Theophylline decreases the effect of the muscle relaxant
    Enoxacin Enoxacin may increase the effect of theophylline.
    Erythromycin The macrolide, erythromycin, may increase the effect and toxicity of theophylline.
    Ethinyl Estradiol The contraceptive increases the effect and toxicity of theophylline
    Ethotoin Decreased effect of both products
    Febuxostat Coadministration of febuxostat with xanthine oxidase substrate drugs (azathioprine, mercaptopurine or theophylline) could increase plasma concentrations of these drugs, since these drugs are metabolized by xanthine oxidase, resulting in severe toxicity; hence their concomitant use is contraindicated. Since febuxostat does not inhibit or induce cytochrome P450 enzymes it lacks significant drug interactions with other drugs metabolized of these enzymes.
    Fluvoxamine Fluvoxamine may increase the therapeutic and adverse effects of theophylline.
    Fosphenytoin Decreased effect of both products
    Grepafloxacin Grepafloxacin may increase the effect of theophylline.
    Halothane Increased risk of cardiac arrhythmia
    Heptabarbital The barbiturate, heptabarbital, decreases the effect of theophylline.
    Hexobarbital The barbiturate, hexobarbital, decreases the effect of theophylline.
    Interferon Alfa-2a, Recombinant Interferon increases the effect and toxicity of theophylline
    Interferon Alfa-2b, Recombinant Interferon increases the effect and toxicity of theophylline
    Interferon alfa-n1 Interferon increases the effect and toxicity of theophylline
    Isoniazid Isoniazid may increase the therapeutic and adverse effects of theophylline.
    Josamycin The macrolide, josamycin, may increase the effect and toxicity of theophylline.
    Lithium Theophylline decreases serum levels of lithium
    Mephenytoin Decreased effect of both products
    Mestranol The contraceptive increases the effect and toxicity of theophylline
    Methohexital The barbiturate, methohexital, decreases the effect of theophylline.
    Methylphenobarbital The barbiturate, methylphenobarbital, decreases the effect of theophylline.
    Metocurine Theophylline decreases the effect of the muscle relaxant
    Mexiletine Mexiletine increases the effect and toxicity of theophylline
    Mivacurium Theophylline decreases the effect of the muscle relaxant
    Nadolol Antagonism of action and increased effect of theophylline
    Norfloxacin Norfloxacin may increase the effect of theophylline.
    Pancuronium Theophylline decreases the effect of the muscle relaxant
    Pefloxacin Pefloxacin may increase the effect of theophylline.
    Peginterferon alfa-2a Interferon increases the effect and toxicity of theophylline
    Peginterferon alfa-2b Interferon increases the effect and toxicity of theophylline
    Penbutolol Antagonism of action and increased effect of theophylline
    Pentobarbital The barbiturate, pentobarbital, decreases the effect of theophylline.
    Pentoxifylline Pentoxifylline increases the effect and toxicity of theophylline
    Phenobarbital The barbiturate, phenobarbital, decreases the effect of theophylline.
    Phenytoin Decreased effect of both products
    Pindolol Antagonism of action and increased effect of theophylline
    Primidone The barbiturate, primidone, decreases the effect of theophylline.
    Propafenone Propafenone increases the effect of theophylline
    Propranolol Antagonism of action and increased effect of theophylline
    Quinidine barbiturate The barbiturate, quinidine barbiturate, decreases the effect of theophylline.
    Regadenoson Non-specific adenosine receptor antagonist may interfere with the vasodilation activity of regadenoson. Avoid methylxanthines for at least 12 hours before administration of regadenoson.
    Rifampin Rifampin decreases the effect of theophylline
    Ritonavir Ritonavir decreases the effect of theophylline
    Rofecoxib Rofecoxib increases the effect and toxicity of theophylline
    Secobarbital The barbiturate, secobarbital, decreases the effect of theophylline.
    Sotalol Antagonism of action and increased effect of theophylline
    St. John's Wort St. John's Wort decreases the effect of theophylline
    Tacrine Tacrine may reduce the elimination rate of Theophylline. Monitor for changes in the therapeutic and toxic effects of theophylline if Tacrine is initiated, discontinued or if the dose is changed.
    Talbutal The barbiturate, talbutal, decreases the effect of theophylline.
    Telithromycin Telithromycin may reduce clearance of Theophylline. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Theophylline if Telithromycin is initiated, discontinued or dose changed.
    Temazepam Theophylline may decrease the efficacy of Temazepam. Monitor for changes in the therapeutic effect of Temazepam if Theophylline is initiated, discontinued or dose changed.
    Terbinafine Terbinafine increases the effect and toxicity of theophylline
    Thiabendazole The strong CYP1A2 inhibitor, Thiabendazole, may increase the effects and toxicity of Theophylline by decreasing Theophylline metabolism and clearance. Monitor for changes in the therapeutic and adverse effects of Theophylline if Thiabendazole is initiated, discontinued or dose changed.
    Ticlopidine Ticlopidine increases the effect and toxicity of theophylline
    Timolol Antagonism of action and increased effect of theophylline
    Tipranavir Tipranavir, co-administered with Ritonavir, may decrease the concentration of Theophylline.
    Troleandomycin The macrolide, troleandomycin, may increase the effect and toxicity of theophylline.
    Tubocurarine Theophylline decreases the effect of the muscle relaxant
    Vecuronium Theophylline decreases the effect of the muscle relaxant
    Verapamil Verapamil increases the effect of theophylline
    Voriconazole Voriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of theophylline by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of theophylline if voriconazole is initiated, discontinued or dose changed.
    Zafirlukast Zafirlukast serum concentrations may be decreased by Theophylline.
    Zileuton Zileuton may increase the therapeutic and adverse effects of theophylline by increasing its serum concentration. Monitor for changes in the therapeutic and adverse effects of theophylline if zileuton is initiated, discontinued or dose changed. Dose alterations should be considered.
    食物相互作用
    • Avoid alcohol.
    • Avoid excessive quantities of coffee or tea (Caffeine).
    • Take with food.

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