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Identification
NameAminophylline
Accession NumberDB01223  (APRD00329)
Typesmall molecule
Groupsapproved
Description

Aminophylline is a drug combination that contains theophylline and ethylenediamine in a 2:1 ratio. Once in the body, theophylline is released and acts as a phosphodiesterase inhibitor, adenosine receptor blocker, and histone deacetylase activator. Similar to other theophyllines, aminophylline is indicated for the treatment of lung diseases such as asthma, chronic bronchitis, and COPD. The majority of aminophylline medications are discontinued and the remaining medications on the market are in short supply.

Structure
Thumb
Synonyms
SynonymLanguageCode
AminophyllinNot AvailableNot Available
SomophyllinNot AvailableNot Available
Theophylline ethylenediamineNot AvailableNot Available
SaltsNot Available
Brand names
NameCompany
MinomalNot Available
PhyllocontinNot Available
SomophyllinNot Available
TruphyllineNot Available
Brand mixtures
Brand NameIngredients
Ami-Nesine LiqAminophylline + Guaifenesin
Quiex - Forte SyrAminophylline + Guaifenesin
Quiex LiqAminophylline + Guaifenesin
Quiex-K1 SyrAminophylline + Guaifenesin + Potassium Iodide
Quiex-Pred SusAminophylline + Guaifenesin + Prednisolone
Categories
CAS number317-34-0
WeightAverage: 420.4264
Monoisotopic: 420.198199306
Chemical FormulaC16H24N10O4
InChI KeyFQPFAHBPWDRTLU-UHFFFAOYSA-N
InChI
InChI=1S/2C7H8N4O2.C2H8N2/c2*1-10-5-4(8-3-9-5)6(12)11(2)7(10)13;3-1-2-4/h2*3H,1-2H3,(H,8,9);1-4H2
IUPAC Name
bis(1,3-dimethyl-2,3,6,7-tetrahydro-1H-purine-2,6-dione); ethane-1,2-diamine
SMILES
NCCN.CN1C2=C(NC=N2)C(=O)N(C)C1=O.CN1C2=C(NC=N2)C(=O)N(C)C1=O
Mass SpecNot Available
Taxonomy
KingdomNot Available
SuperclassNot Available
ClassNot Available
SubclassNot Available
Direct parentNot Available
Alternative parentsNot Available
SubstituentsNot Available
Classification descriptionNot Available
Pharmacology
IndicationFor the treatment of bronchospasm due to asthma, emphysema and chronic bronchitis.
PharmacodynamicsAminophylline is the ethylenediamine salt of theophylline. Theophylline stimulates the CNS, skeletal muscles, and cardiac muscle. It relaxes certain smooth muscles in the bronchi, produces diuresis, and causes an increase in gastric secretion.
Mechanism of actionAminophylline is the ethylenediamine salt of theophylline. After ingestion, theophylline is released from aminophylline, and 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.
AbsorptionNot Available
Volume of distribution
  • 0.3 to 0.7 L/kg
Protein binding60%
Metabolism
Route of eliminationNot Available
Half life7-9 hours
Clearance
  • 0.29 mL/kg/min [postnatal age 3-15 days]
  • 0.64 mL/kg/min [postnatal age 25-57 days]
  • 1.7 mL/kg/min [ 1-4 years]
  • 1.6 mL/kg/min [4-12 years]
  • 0.9 mL/kg/min [13-15 years]
  • 1.4 mL/kg/min [16-17 years]
  • 0.65 mL/kg/min [Adults (16-60 years), non-smoking asthmatics]
  • 0.41 mL/kg/min [Elderly (>60 years). 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 -cholestasis]
  • 0.35 mL/kg/min [cirrhosis]
  • 0.65 mL/kg/min [acute hepatitis]
  • 0.47 mL/kg/min [Sepsis with multi-organ failure]
  • 0.38 mL/kg/min [hypothyroid]
  • 0.8 mL/kg/min [hyperthyroid]
ToxicityNot Available
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 0.9778
Blood Brain Barrier + 0.5908
Caco-2 permeable - 0.6802
P-glycoprotein substrate Substrate 0.7341
P-glycoprotein inhibitor I Non-inhibitor 0.9164
P-glycoprotein inhibitor II Non-inhibitor 0.9673
Renal organic cation transporter Non-inhibitor 0.7935
CYP450 2C9 substrate Non-substrate 0.8073
CYP450 2D6 substrate Non-substrate 0.8093
CYP450 3A4 substrate Substrate 0.5482
CYP450 1A2 substrate Non-inhibitor 0.8726
CYP450 2C9 substrate Non-inhibitor 0.9332
CYP450 2D6 substrate Non-inhibitor 0.9633
CYP450 2C19 substrate Non-inhibitor 0.9184
CYP450 3A4 substrate Non-inhibitor 0.8031
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.8858
Ames test Non AMES toxic 0.6724
Carcinogenicity Non-carcinogens 0.8696
Biodegradation Not ready biodegradable 0.9149
Rat acute toxicity 2.4979 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.7876
hERG inhibition (predictor II) Inhibitor 0.6143
Pharmacoeconomics
Manufacturers
  • Fisons corp
  • Gd searle llc
  • Abraxis pharmaceutical products
  • Elkins sinn div ah robins co inc
  • Hospira inc
  • International medication system
  • International medication systems ltd
  • King pharmaceuticals inc
  • Luitpold pharmaceuticals inc
  • Pharma serve inc sub torigian laboratories
  • Smith and nephew solopak div smith and nephew
  • Teva parenteral medicines inc
  • Morton grove pharmaceuticals inc
  • Roxane laboratories inc
  • Actavis mid atlantic llc
  • G and w laboratories inc
  • Impax laboratories inc
  • Tablicaps inc
  • Vale chemical co inc
  • Pharmaceutical research assoc inc
  • Ascot hosp pharmaceuticals inc div travenol laboratories inc
  • Barr laboratories inc
  • Duramed pharmaceuticals inc sub barr laboratories inc
  • Halsey drug co inc
  • Kv pharmaceutical co
  • Lannett co inc
  • Pal pak inc
  • Panray corp sub ormont drug and chemical co inc
  • Purepac pharmaceutical co
  • Sandoz inc
  • Valeant pharmaceuticals international
  • Vangard laboratories inc div midway medical co
  • Vintage pharmaceuticals inc
  • Watson laboratories inc
  • West ward pharmaceutical corp
Packagers
Dosage forms
FormRouteStrength
SolutionIntravenous
TabletOral
Tablet, extended releaseOral
Prices
Unit descriptionCostUnit
Aminophylline 250 mg/10 ml vial0.48USDml
Aminophylline 25 mg/ml0.41USDml
Phyllocontin-350 350 mg Sustained-Release Tablet0.31USDtablet
Aminophylline 100 mg tablet0.26USDtablet
Phyllocontin 225 mg Sustained-Release Tablet0.24USDtablet
Aminophylline powder0.17USDg
Aminophylline 200 mg tablet0.15USDtablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
Statesolid
Experimental Properties
PropertyValueSource
water solubility2E+005 mg/LMERCK INDEX (1996)
logP-3.03Not Available
Predicted Properties
PropertyValueSource
logP-0.77ChemAxon
pKa (strongest acidic)7.82ChemAxon
pKa (strongest basic)-0.78ChemAxon
physiological charge0ChemAxon
hydrogen acceptor count3ChemAxon
hydrogen donor count1ChemAxon
polar surface area69.3ChemAxon
rotatable bond count1ChemAxon
refractivity44.93ChemAxon
polarizability16.86ChemAxon
number of rings4ChemAxon
bioavailability1ChemAxon
rule of fiveYesChemAxon
Ghose filterNoChemAxon
Veber's ruleNoChemAxon
MDDR-like ruleNoChemAxon
Spectra
SpectraNot Available
References
Synthesis ReferenceNot Available
General ReferenceNot Available
External Links
ResourceLink
KEGG DrugD00227
PubChem Compound9433
PubChem Substance46508784
ChemSpider9062
Therapeutic Targets DatabaseDAP000613
PharmGKBPA164781029
Drug Product Database582662
Drugs.comhttp://www.drugs.com/cdi/aminophylline.html
WikipediaAminophylline
ATC CodesNot Available
AHFS Codes
  • 86:16.00
PDB EntriesNot Available
FDA labelNot Available
MSDSshow(72.7 KB)
Interactions
Drug Interactions
Drug
AciclovirAcyclovir increases the effect and toxicity of theophylline
AdenosineThis xanthine decreases the effect of adenosine
AmobarbitalThe barbiturate, amobarbital, decreases the effect of aminophylline.
AprobarbitalThe barbiturate, aprobarbital, decreases the effect of aminophylline.
AtracuriumTheophylline decreases the effect of muscle relaxant
BromazepamAminophylline may decrease the therapeutic effect of bromazepam. Monitor for changes in the therapeutic effects of bromazepam if aminophylline is initiated, discontinued or dose changed.
ButabarbitalThe barbiturate, butabarbital, decreases the effect of aminophylline.
ButalbitalThe barbiturate, butalbital, decreases the effect of aminophylline.
ButethalThe barbiturate, butethal, decreases the effect of aminophylline.
CarbamazepineCarbamazepine may decrease the serum concentration of aminophylline. Aminophylline 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.
CarteololAntagonism of action and increased effect of theophylline
CimetidineCimetidine may increase the serum concentration of aminophylline by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of aminophylline if cimetidine is initiated, discontinued or dose changed.
CiprofloxacinCiprofloxacin may increase the effect of aminophylline.
ClarithromycinClarithromycin may increase the effect amd toxicity of aminophylline.
Dihydroquinidine barbiturateThe barbiturate, dihydroquinidine barbiturate, decreases the effect of aminophylline.
DisulfiramDisulfiram may increase the effect and toxicity of aminophylline.
Doxacurium chlorideTheophylline decreases the effect of muscle relaxant
EnoxacinEnoxacin may increase the effect of aminophylline.
ErythromycinThe macrolide, erythromycin, may increase the effect and toxicity of the theophylline derivative, aminophylline.
Ethinyl EstradiolThe contraceptive increases the effect and toxicity of theophylline
EthotoinDecreased effect of both products
FluvoxamineFluvoxamine may increase the effect and toxicity of aminophylline.
FosphenytoinDecreased effect of both products
GrepafloxacinGrepafloxacin may increase the effect of aminophylline.
HalothaneIncreased risk of cardiac arrhythmia
HeptabarbitalThe barbiturate, heptabarbital, decreases the effect of aminophylline.
HexobarbitalThe barbiturate, hexobarbital, decreases the effect of aminophylline.
Interferon Alfa-2a, RecombinantInterferon increases the effect and toxicity of theophylline
Interferon Alfa-2b, RecombinantInterferon increases the effect and toxicity of theophylline
Interferon alfa-n1Interferon increases the effect and toxicity of theophylline
IsoniazidIsoniazid may increase the effect and toxicity of oxtriphylline.
JosamycinThe macrolide, josamycin, may increase the effect and toxicity of the theophylline derivative, aminophylline.
LithiumTheophylline decreases serum levels of lithium
MephenytoinDecreased effect of both products
MestranolThe contraceptive increases the effect and toxicity of theophylline
MethohexitalThe barbiturate, methohexital, decreases the effect of aminophylline.
MethylphenobarbitalThe barbiturate, methylphenobarbital, decreases the effect of aminophylline.
MetocurineTheophylline decreases the effect of muscle relaxant
MexiletineMexiletine increases the effect and toxicity of theophylline
MivacuriumTheophylline decreases the effect of muscle relaxant
NadololAntagonism of action and increased effect of theophylline
NorfloxacinNorfloxacin may increase the effect of aminophylline.
PancuroniumTheophylline decreases the effect of muscle relaxant
PefloxacinPefloxacin may increase the effect of aminophylline.
Peginterferon alfa-2aInterferon increases the effect and toxicity of theophylline
Peginterferon alfa-2bInterferon increases the effect and toxicity of theophylline
PenbutololAntagonism of action and increased effect of theophylline
PentobarbitalThe barbiturate, pentobarbital, decreases the effect of aminophylline.
PentoxifyllinePentoxifylline may increase the effect and toxicity of aminophylline.
PhenobarbitalThe barbiturate, phenobarbital, decreases the effect of aminophylline.
PhenytoinDecreased effect of both products
PindololAntagonism of action and increased effect of theophylline
PrimidoneThe barbiturate, primidone, decreases the effect of aminophylline.
PropafenonePropafenone increases the effect of theophylline
PropranololAntagonism of action and increased effect of theophylline
Quinidine barbiturateThe barbiturate, quinidine barbiturate, decreases the effect of aminophylline.
RegadenosonReduces duration of >2-fold increase in peak flow velocity. No effect on heart rate increase.
RifampicinRifampin decreases the effect of theophylline
RitonavirRitonavir decreases the effect of theophylline
RofecoxibRofecoxib increases the effect and toxicity of theophylline
SecobarbitalThe barbiturate, secobarbital, decreases the effect of aminophylline.
SotalolAntagonism of action and increased effect of theophylline
St. John's WortSt. John's Wort decreases the effect of theophylline
TacrineTacrine may reduce the elimination rate of Aminophylline. Monitor for changes in the therapeutic and toxic effects of theophylline if Tacrine is initiated, discontinued or if the dose is changed.
TalbutalThe barbiturate, talbutal, decreases the effect of aminophylline.
TemazepamAminophylline may decrease the efficacy of Temazepam. Monitor for changes in the therapeutic effect of Temazepam if Aminophylline is initiated, discontinued or dose changed.
TerbinafineTerbinafine increases the effect and toxicity of theophylline
ThiabendazoleThe strong CYP1A2 inhibitor, Thiabendazole, may increase the effects and toxicity of Aminophylline by decreasing Aminophylline metabolism and clearance. Monitor for changes in the therapeutic and adverse effects of Aminophylline if Thiabendazole is initiated, discontinued or dose changed.
TiclopidineTiclopidine increases the effect and toxicity of theophylline
TimololAntagonism of action and increased effect of theophylline
TroleandomycinThe macrolide, troleandomycin, may increase the effect and toxicity of theophylline derivative, aminophylline.
TubocurarineTheophylline decreases the effect of muscle relaxant
VecuroniumTheophylline decreases the effect of muscle relaxant
VerapamilVerapamil increases the effect of theophylline
ZafirlukastZafirlukast serum concentrations may be decreased by the theophylline derivative Aminophylline.
ZileutonZileuton increases the effect and toxicity of theophylline
Food Interactions
  • Limit caffeine intake.
  • Take with food.
  • Vitamin B6 needs increased, supplement recommended.

Targets

1. cGMP-inhibited 3',5'-cyclic phosphodiesterase A

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
cGMP-inhibited 3',5'-cyclic phosphodiesterase A Q14432 Details

References:

  1. Hirota K, Yoshioka H, Kabara S, Koizumi Y, Abe H, Sato T, Matsuki A: Spasmolytic effects of colforsin daropate on serotonin-induced pulmonary hypertension and bronchoconstriction in dogs. Acta Anaesthesiol Scand. 2002 Mar;46(3):297-302. Pubmed
  2. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

2. Adenosine receptor A1

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: antagonist

Components

Name UniProt ID Details
Adenosine receptor A1 P30542 Details

References:

  1. Yamamoto S, Nakanishi O, Matsui T, Shinohara N, Kinoshita H, Lambert C, Ishikawa T: Intrathecal adenosine A1 receptor agonist attenuates hyperalgesia without inhibiting spinal glutamate release in the rat. Cell Mol Neurobiol. 2003 Apr;23(2):175-85. Pubmed
  2. Lerman BB: Response of nonreentrant catecholamine-mediated ventricular tachycardia to endogenous adenosine and acetylcholine. Evidence for myocardial receptor-mediated effects. Circulation. 1993 Feb;87(2):382-90. Pubmed

3. Adenosine receptor A3

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: antagonist

Components

Name UniProt ID Details
Adenosine receptor A3 P33765 Details

References:

  1. Stella L, de Novellis V, Marabese I, Berrino L, Maione S, Filippelli A, Rossi F: The role of A3 adenosine receptors in central regulation of arterial blood pressure. Br J Pharmacol. 1998 Oct;125(3):437-40. Pubmed

4. Histone deacetylase 2

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: activator

Components

Name UniProt ID Details
Histone deacetylase 2 Q92769 Details

References:

  1. Ito K, Lim S, Caramori G, Cosio B, Chung KF, Adcock IM, Barnes PJ: A molecular mechanism of action of theophylline: Induction of histone deacetylase activity to decrease inflammatory gene expression. Proc Natl Acad Sci U S A. 2002 Jun 25;99(13):8921-6. Epub 2002 Jun 17. Pubmed

Enzymes

1. Cytochrome P450 1A2

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 1A2 P05177 Details

References:

  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

2. Cytochrome P450 2E1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 2E1 P05181 Details

References:

  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

3. Cytochrome P450 3A4

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 3A4 P08684 Details

References:

  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

Comments
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Drug created on June 13, 2005 07:24 / Updated on September 16, 2013 17:13