Banner
Identification
Name Theophylline
Accession Number DB00277 (APRD00082)
Type small molecule
Groups approved
Description

A methyl xanthine derivative from tea with diuretic, smooth muscle relaxant, bronchial dilation, cardiac and central nervous system stimulant activities. Theophylline inhibits the 3',5'-cyclic nucleotide phosphodiesterase that degrades cyclic AMP thus potentiates the actions of agents that act through adenylate cyclase and cyclic AMP. [PubChem]
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
  • Dimethylxanthine
  • Pseudotheophylline
  • Theophyline
  • Theophyllin
  • Theophylline aminoacetate
  • Theophylline Anhydrous
Brand names
  • Accurbron
  • Acet-Theocin
  • Aerobin
  • Aerolate
  • Aerolate III
  • Aerolate SR
  • Afonilm
  • Afonilum
  • Aquaphyllin
  • Armophylline
  • Asbron
  • Asmalix
  • Asmax
  • Austyn
  • Bilordyl
  • Bronchoretard
  • Bronkodyl
  • Bronkodyl SR
  • Cetraphylline
  • Choledyl SA
  • Chronophyllin
  • Constant T
  • Diffumal
  • Diphyllin
  • Doraphyllin
  • Duraphyl
  • Duraphyllin
  • Dyspne-Inhal
  • Egifilin
  • Elan
  • Elixex
  • Elixicon
  • Elixomin
  • Elixophyllin
  • Elixophyllin SR
  • Elixophylline
  • Etheophyl
  • Euphyllin
  • Euphylline
  • Euphylong
  • Labid
  • Lanophyllin
  • Lasma
  • Liquophylline
  • Liquorice
  • Maphylline
  • Medaphyllin
  • Nuelin
  • Optiphyllin
  • Parkophyllin
  • Physpan
  • Pro-Vent
  • Pulmidur
  • Pulmo-Timelets
  • Quibron
  • Quibron T
  • Quibron T/SR
  • Quibron-T
  • Quibron-T/SR
  • Respbid
  • Respicur
  • Respid
  • Slo-Bid
  • Slo-Phyllin
  • Solosin
  • Somophyllin CRT
  • Somophyllin T
  • Somophyllin-CRT
  • Somophyllin-DF
  • Somophyllin-T
  • Spophyllin Retard
  • Sustaire
  • Synophylate
  • Synophylate-L.A. Cenules
  • T-Phyl
  • Talotren
  • Tefamin
  • Telb-DS
  • Telbans Dry Syrup
  • Teocen 200
  • Teofilina
  • Teofyllamin
  • Teolair
  • Teonova
  • Teosona
  • Tesona
  • Theacitin
  • Theal Tablets
  • Theo 24
  • Theo-11
  • Theo-24
  • Theo-DS
  • Theo-Dur
  • Theo-Nite
  • Theo-Sav
  • Theobid
  • Theobid Duracap
  • Theobid Jr.
  • Theochron
  • Theocin
  • Theoclair-SR
  • Theoclear
  • Theoclear 80
  • Theoclear L.A.-130
  • Theoclear LA
  • Theoclear-200
  • Theoclear-80
  • Theocontin
  • Theodel
  • Theodrip
  • Theodur Dry Syrup
  • Theofol
  • Theograd
  • Theolair
  • Theolair-SR
  • Theolix
  • Theolixir
  • Theon
  • Theona P
  • Theopek
  • Theophyl
  • Theophyl-225
  • Theophyl-SR
  • Theophylline-SR
  • Theoplus
  • Theospan
  • Theostat
  • Theostat 80
  • Theotard
  • Theovent
  • Uni-Dur
  • Unifyl
  • Unilong
  • Uniphyl
  • Uniphyllin
  • Xanthium
  • Xantivent
Brand name mixtures
  • Bronchyl Syrup (alcohol anhydrous + beechwood creosote + cocillana + eucalyptus + guaiacol oleate + ipecac + lobelia inflata + menthol + myroxylon balsamum + theophylline + white pine)
  • Choledyl Expectorant Elixir (guaifenesin + oxtriphylline)
  • Diuerb tab (oil of fleabane + theophylline + urea)
  • IDM Expectorant tab (guaifenesin + potassium iodide + pyrilamine maleate + theophylline)
  • IDM tab (potassium iodide + pyrilamine maleate + theophylline)
  • PMS-Oxtriphylline Elixir (alcohol anhydrous + oxtriphylline)
  • Pulmo Septol Sirop (beechwood creosote + cocillana + eucalyptus oil + guaiacol + ipecac + lobelia inflata + myroxylon balsamum + theophylline + white pine)
  • Ratio-theo-bronc (guaifenesin + potassium iodide + pyrilamine maleate + theophylline)
  • Tedral tab (l-ephedrine hydrochloride + phenobarbital + theophylline)
  • Theophylline 0.8mg and 5% dextrose inj (dextrose + theophylline)
  • Theophylline 0.8mg/ml in 5% dextrose inj (dextrose + theophylline)
  • Theophylline 1.6mg and 5% dextrose inj (dextrose + theophylline)
  • Theophylline 4mg and 5% dextrose inj (dextrose + theophylline)
  • Theophylline rougier elixir (alcohol anhydrous + theophylline)
Categories
  • Vasodilator Agents
  • Phosphodiesterase Inhibitors
  • Bronchodilator Agents
  • Respiratory Smooth Muscle Relaxants
CAS number 58-55-9
Weight Average: 180.164
Monoisotopic: 180.064725520
Chemical Formula C7H8N4O2
InChI Key InChIKey=ZFXYFBGIUFBOJW-UHFFFAOYSA-N
InChI
InChI=1S/C7H8N4O2/c1-10-5-4(8-3-9-5)6(12)11(2)7(10)13/h3H,1-2H3,(H,8,9)
Plain Text
IUPAC Name
1,3-dimethyl-2,3,6,7-tetrahydro-1H-purine-2,6-dione
SMILES
CN1C2=C(NC=N2)C(=O)N(C)C1=O
Plain Text
Mass Spec show (3 KB)
Taxonomy
Kingdom Organic
Classes
  • Xanthines
Substructures
  • Xanthines
  • Pyrimidines and Derivatives
  • Imidazoles
  • Heterocyclic compounds
  • Aromatic compounds
  • Purines and Purine Derivatives
  • Cyanamides
Pharmacology
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.
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.

Enzyme Metabolite Reaction Km Vmax
Cytochrome P450 1A2 1-methylxanthine 3-N-demethylation 1930 0.0025
Cytochrome P450 1A2 3-methylxanthine 1-N-demethylation 2050 0.0023
Cytochrome P450 2E1 1,3-dimethyluric acid 8-hydroxylation 5340 0.023
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
Pharmacoeconomics
Manufacturers
  • Fleming and co pharmaceuticals inc
  • Forest laboratories inc
  • Sanofi aventis us llc
  • Dm graham laboratories inc
  • Ucb inc
  • Whitby pharmaceuticals inc
  • Schwarz pharma inc
  • Schering corp
  • Central pharmaceuticals inc
  • Hospira inc
  • Inwood laboratories inc sub forest laboratories inc
  • Sandoz inc
  • Rp scherer north america div rp scherer corp
  • Ortho mcneil pharmaceutical inc
  • Schering corp sub schering plough corp
  • Fisons corp
  • Kv pharmaceutical co
  • Rp scherer north america
  • Hr cenci laboratories inc
  • Caraco pharmaceutical laboratories ltd
  • Lannett co inc
  • Panray corp sub ormont drug and chemical co inc
  • Alpharma us pharmaceuticals division
  • Cenci powder products inc
  • Halsey drug co inc
  • L perrigo co
  • Pharmaceutical assoc inc div beach products
  • Precision dose inc
  • Roxane laboratories inc
  • Taro pharmaceuticals usa inc
  • Wockhardt eu operations (swiss) ag
  • B braun medical inc
  • Baxter healthcare corp
  • 3m pharmaceuticals inc
  • Ferndale laboratories inc
  • Warner chilcott co llc
  • Monarch pharmaceuticals inc
  • Roerig div pfizer inc
  • Able laboratories inc
  • Glenmark generics ltd
  • Nostrum pharmaceuticals inc
  • Pliva inc
  • Pharmaceutical research assoc inc
  • Purdue pharmaceutical products lp
  • Graceway pharmaceuticals llc
  • Novartis consumer health inc
Packagers
Dosage forms
Form Route Strength
Elixir Oral
Liquid Oral
Solution Intravenous
Tablet Oral
Tablet, extended release Oral
Prices
Unit description Cost Unit
Elixophyllin GG 100-100 mg/15ml Solution 240ml Bottle 60.98 USD bottle
Uniphyl 600 mg 24 Hour tablet 2.28 USD tablet
Theo-24 400 mg 24 Hour Capsule 2.04 USD capsule
Theo-24 400 mg capsule sa 1.97 USD capsule
Uniphyl 400 mg 24 Hour tablet 1.58 USD tablet
Theo-24 300 mg 24 Hour Capsule 1.45 USD capsule
Theo-24 300 mg capsule sa 1.4 USD capsule
Theophylline 400 mg 24 Hour tablet 1.27 USD tablet
Theo-24 200 mg 24 Hour Capsule 1.25 USD capsule
Theo-24 200 mg capsule sa 1.14 USD capsule
Theochron 450 mg tablet sa 0.94 USD tablet
Theophylline CR 300 mg 12 Hour Capsule 0.93 USD capsule
Theo-24 100 mg 24 Hour Capsule 0.83 USD capsule
Theophylline CR 200 mg 12 Hour Capsule 0.79 USD capsule
Theophylline CR 450 mg 12 Hour tablet 0.79 USD tablet
Theo-24 100 mg capsule sa 0.76 USD capsule
Quibron 90-150 mg capsule 0.73 USD capsule
Theophylline CR 125 mg 12 Hour Capsule 0.73 USD capsule
Uniphyl 600 mg Sustained-Release Tablet 0.68 USD tablet
Uniphyl 400 mg Sustained-Release Tablet 0.56 USD tablet
Theochron 300 mg tablet sa 0.54 USD tablet
Theophylline CR 300 mg 12 Hour tablet 0.51 USD tablet
Theophylline CR 200 mg 12 Hour tablet 0.4 USD tablet
Theochron 200 mg tablet sa 0.33 USD tablet
Theophylline CR 100 mg 12 Hour tablet 0.3 USD tablet
Elixophyllin GG 100-100 mg/15ml Solution 0.24 USD ml
Theochron 100 mg tablet sa 0.23 USD tablet
Elixophyllin 80 mg/15ml Elixir 0.2 USD ml
Elixophyllin 80 mg/15 ml elix 0.19 USD ml
Apo-Theo La 300 mg Sustained-Release Tablet 0.15 USD tablet
Apo-Theo La 100 mg Sustained-Release Tablet 0.14 USD tablet
Apo-Theo La 200 mg Sustained-Release Tablet 0.14 USD tablet
Theophylline anhydrous powder 0.08 USD g
Theophylline 200 mg/100 ml d5w 0.06 USD ml
Theolair 5.3 mg/ml Liquid 0.03 USD ml
Patents Not Available
Properties
State solid
Melting point 272 oC
Experimental Properties
Property Value Source
water solubility 1-5 g/L PhysProp
logP -0.8 PhysProp
Caco2 permeability -4.35 [ADME Research, USCD] BiGG
pKa 8.81 Various sources
Predicted Properties
Property Value Source
water solubility 2.29e+01 g/l ALOGPS
logP -0.26 ALOGPS
logP -0.77 ChemAxon Molconvert
logS -0.90 ALOGPS
pKa ChemAxon Molconvert
hydrogen acceptor count 3 ChemAxon Molconvert
hydrogen donor count 1 ChemAxon Molconvert
polar surface area 69.30 ChemAxon Molconvert
rotatable bond count 0 ChemAxon Molconvert
refractivity 44.93 ChemAxon Molconvert
polarizability 16.86 ChemAxon Molconvert
References
Synthesis Reference Not Available
General Reference Not Available
External Links
Resource Link
KEGG Drug D00371 Link_out
KEGG Compound C07130 Link_out
PubChem Compound 2153 Link_out
PubChem Substance 46505949 Link_out
ChemSpider 2068 Link_out
BindingDB 10847 Link_out
ChEBI 28177 Link_out
ChEMBL 28177 Link_out
Therapeutic Targets Database DAP000002 Link_out
PharmGKB PA451647 Link_out
HET TEP Link_out
Drug Product Database 627410 Link_out
RxList http://www.rxlist.com/cgi/generic/theosr.htm Link_out
Drugs.com http://www.drugs.com/cdi/theophylline.html Link_out
PDRhealth http://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/the1440.shtml Link_out
Wikipedia http://en.wikipedia.org/wiki/Theophylline Link_out
ATC Codes
  • R03DA04
  • R03DA05
AHFS Codes
  • 86:16.00
PDB Entries Not Available
FDA label show (85.2 KB)
MSDS show (75.1 KB)
Interactions
Drug Interactions Not Available
Food Interactions
  • Avoid alcohol.
  • Avoid excessive quantities of coffee or tea (Caffeine).
  • Take with food.
Targets

1. Adenosine A1 receptor

Pharmacological action: yes
Actions: antagonist

Receptor for adenosine. The activity of this receptor is mediated by G proteins which inhibit adenylyl cyclase

Organism class: human
UniProt ID: P30542 Link_out
Gene: ADORA1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Nantwi KD, Basura GJ, Goshgarian HG: Adenosine A1 receptor mRNA expression and the effects of systemic theophylline administration on respiratory function 4 months after C2 hemisection. J Spinal Cord Med. 2003 Winter;26(4):364-71. Pubmed
  2. Daly JW, Jacobson KA, Ukena D: Adenosine receptors: development of selective agonists and antagonists. Prog Clin Biol Res. 1987;230:41-63. Pubmed

2. Adenosine A2a receptor

Pharmacological action: yes
Actions: antagonist

Receptor for adenosine. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase

Organism class: human
UniProt ID: P29274 Link_out
Gene: ADORA2A Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Pechlivanova DM, Georgiev VP: Effects of single and long-term theophylline treatment on the threshold of mechanical nociception: contribution of adenosine A1 and alpha2-adrenoceptors. Methods Find Exp Clin Pharmacol. 2005 Nov;27(9):659-64. Pubmed
  2. Daly JW, Jacobson KA, Ukena D: Adenosine receptors: development of selective agonists and antagonists. Prog Clin Biol Res. 1987;230:41-63. Pubmed

3. Adenosine A2b receptor

Pharmacological action: yes
Actions: antagonist

Receptor for adenosine. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase

Organism class: human
UniProt ID: P29275 Link_out
Gene: ADORA2B Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
  2. Philipp S, Yang XM, Cui L, Davis AM, Downey JM, Cohen MV: Postconditioning protects rabbit hearts through a protein kinase C-adenosine A2b receptor cascade. Cardiovasc Res. 2006 May 1;70(2):308-14. Epub 2006 Feb 23. Pubmed
  3. Phelps PT, Anthes JC, Correll CC: Characterization of adenosine receptors in the human bladder carcinoma T24 cell line. Eur J Pharmacol. 2006 Apr 24;536(1-2):28-37. Epub 2006 Mar 3. Pubmed
  4. Fozard JR, Baur F, Wolber C: Antagonist pharmacology of adenosine A2B receptors from rat, guinea pig and dog. Eur J Pharmacol. 2003 Aug 15;475(1-3):79-84. Pubmed
  5. Holgate ST: The Quintiles Prize Lecture 2004. The identification of the adenosine A2B receptor as a novel therapeutic target in asthma. Br J Pharmacol. 2005 Aug;145(8):1009-15. Pubmed
  6. Daly JW, Jacobson KA, Ukena D: Adenosine receptors: development of selective agonists and antagonists. Prog Clin Biol Res. 1987;230:41-63. Pubmed

4. cAMP-specific 3',5'-cyclic phosphodiesterase 4B

Pharmacological action: yes
Actions: inhibitor

May be involved in mediating central nervous system effects of therapeutic agents ranging from antidepressants to antiasthmatic and anti-inflammatory agents

Organism class: human
UniProt ID: Q07343 Link_out
Gene: PDE4B Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Lipworth BJ: Phosphodiesterase-4 inhibitors for asthma and chronic obstructive pulmonary disease. Lancet. 2005 Jan 8-14;365(9454):167-75. Pubmed

5. cGMP-specific 3',5'-cyclic phosphodiesterase

Pharmacological action: yes
Actions: inhibitor

Plays a role in signal transduction by regulating the intracellular concentration of cyclic nucleotides. This phosphodiesterase catalyzes the specific hydrolysis of cGMP to 5'- GMP

Organism class: human
UniProt ID: O76074 Link_out
Gene: PDE5A Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

6. cAMP-specific 3',5'-cyclic phosphodiesterase 4A

Pharmacological action: yes
Actions: inhibitor

Adenosine 3',5'-cyclic phosphate + H(2)O = adenosine 5'-phosphate

Organism class: human
UniProt ID: P27815 Link_out
Gene: PDE4A Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Wang K, Chen JQ, Chen Z, Chen JC: Inhibition of human phosphodiesterase 4A expressed in yeast cell GL62 by theophylline, rolipram, and acetamide-45. Acta Pharmacol Sin. 2002 Nov;23(11):1013-7. Pubmed
  2. Haider S: Cyclic AMP level and phosphodiesterase activity during 17alpha,20beta-dihydroxy-4-pregnen-3-one induction and theophylline inhibition of oocyte maturation in the catfish, Clarias batrachus. Comp Biochem Physiol A Mol Integr Physiol. 2003 Feb;134(2):267-74. Pubmed
  3. Rickards KJ, Andrews MJ, Waterworth TH, Alexander GB, Cunningham FM: Differential effects of phosphodiesterase inhibitors on platelet activating factor (PAF)- and adenosine diphosphate (ADP)-induced equine platelet aggregation. J Vet Pharmacol Ther. 2003 Aug;26(4):277-82. Pubmed
  4. Usta C, Sadan G, Tuncel B: The effect of the indomethacin on phosphodiesterase inhibitors mediated responses in isolated trachea preparations. Prostaglandins Leukot Essent Fatty Acids. 2004 Sep;71(3):137-41. Pubmed
  5. Lee JM, Zemans RL, Hejazi M, Chin BB, Ladenson PW, Caturegli P: Modulation of thyroidal radioiodine uptake by theophylline. Exp Mol Pathol. 2004 Oct;77(2):116-20. Pubmed

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

Pharmacological action: yes
Actions: inhibitor

Hydrolyzes both cyclic AMP (cAMP) and cyclic GMP (cGMP)

Organism class: human
UniProt ID: Q14432 Link_out
Gene: PDE3A Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Rickards KJ, Andrews MJ, Waterworth TH, Alexander GB, Cunningham FM: Differential effects of phosphodiesterase inhibitors on platelet activating factor (PAF)- and adenosine diphosphate (ADP)-induced equine platelet aggregation. J Vet Pharmacol Ther. 2003 Aug;26(4):277-82. Pubmed
  2. Wu BN, Lin RJ, Lo YC, Shen KP, Wang CC, Lin YT, Chen IJ: KMUP-1, a xanthine derivative, induces relaxation of guinea-pig isolated trachea: the role of the epithelium, cyclic nucleotides and K+ channels. Br J Pharmacol. 2004 Aug;142(7):1105-14. Epub 2004 Jul 5. Pubmed
  3. Kajikawa S, Kigami D, Nakayama H, Doi K: Changes in submaxillary gland gene expression in F344 rats by multiple dosing of theophylline. Exp Anim. 2006 Apr;55(2):143-6. Pubmed
Enzymes

1. Cytochrome P450 3A4

Actions: substrate

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4- hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. The enzyme also hydroxylates etoposide

UniProt ID: P08684 Link_out
Gene: CYP3A4
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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 1A2

Actions: substrate, inhibitor

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Most active in catalyzing 2-hydroxylation. Caffeine is metabolized primarily by cytochrome CYP1A2 in the liver through an initial N3-demethylation. Also acts in the metabolism of aflatoxin B1 and acetaminophen

UniProt ID: P05177 Link_out
Gene: CYP1A2
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Brosen K: Drug interactions and the cytochrome P450 system. The role of cytochrome P450 1A2. Clin Pharmacokinet. 1995;29 Suppl 1:20-5. Pubmed
  2. Wang B, Zhou SF: Synthetic and natural compounds that interact with human cytochrome P450 1A2 and implications in drug development. Curr Med Chem. 2009;16(31):4066-218. Pubmed
  3. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
  4. 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
  5. Sarkar MA, Hunt C, Guzelian PS, Karnes HT: Characterization of human liver cytochromes P-450 involved in theophylline metabolism. Drug Metab Dispos. 1992 Jan-Feb;20(1):31-7. Pubmed

3. Adenosine deaminase

Actions: inhibitor, inducer

Adenosine + H(2)O = inosine + NH(3)

UniProt ID: P00813 Link_out
Gene: ADA Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Saboury AA, Bagheri S, Ataie G, Amanlou M, Moosavi-Movahedi AA, Hakimelahi GH, Cristalli G, Namaki S: Binding properties of adenosine deaminase interacted with theophylline. Chem Pharm Bull (Tokyo). 2004 Oct;52(10):1179-82. Pubmed
  2. Singh LS, Sharma R: Purification and characterization of intestinal adenosine deaminase from mice. Mol Cell Biochem. 2000 Jan;204(1-2):127-34. Pubmed
  3. Bandyopadhyay BC, Poddar MK: Theophylline-induced changes in mammalian adenosine deaminase activity and corticosterone status: possible relation to immune response. Methods Find Exp Clin Pharmacol. 1997 Apr;19(3):181-4. Pubmed

4. Cytochrome P450 2E1

Actions: substrate

Metabolizes several precarcinogens, drugs, and solvents to reactive metabolites. Inactivates a number of drugs and xenobiotics and also bioactivates many xenobiotic substrates to their hepatotoxic or carcinogenic forms

UniProt ID: P05181 Link_out
Gene: CYP2E1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
  2. 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. Sarkar MA, Hunt C, Guzelian PS, Karnes HT: Characterization of human liver cytochromes P-450 involved in theophylline metabolism. Drug Metab Dispos. 1992 Jan-Feb;20(1):31-7. Pubmed

5. Cytochrome P450 1A1

Actions: substrate, inhibitor

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics

UniProt ID: P04798 Link_out
Gene: CYP1A1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

6. Cytochrome P450 1B1

Actions: substrate

Participates in the metabolism of an as-yet-unknown biologically active molecule that is a participant in eye development

UniProt ID: Q16678 Link_out
Gene: CYP1B1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

7. Cytochrome P450 2C8

Actions: substrate

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. In the epoxidation of arachidonic acid it generates only 14,15- and 11,12-cis-epoxyeicosatrienoic acids. It is the principal enzyme responsible for the metabolism the anti- cancer drug paclitaxel (taxol)

UniProt ID: P10632 Link_out
Gene: CYP2C8
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

8. Cytochrome P450 2C9

Actions: substrate

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. This enzyme contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S- warfarin, diclofenac, phenytoin, tolbutamide and losartan

UniProt ID: P11712 Link_out
Gene: CYP2C9
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

9. Cytochrome P450 2D6

Actions: substrate

Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants

UniProt ID: P10635 Link_out
Gene: CYP2D6 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
Transporters

1. Solute carrier family 22 member 7

Actions: inhibitor

Mediates sodium-independent multispecific organic anion transport. Transport of prostaglandin E2, prostaglandin F2, tetracycline, bumetanide, estrone sulfate, glutarate, dehydroepiandrosterone sulfate, allopurinol, 5-fluorouracil, paclitaxel, L-ascorbic acid, salicylate, ethotrexate, and alpha- ketoglutarate

UniProt ID: Q9Y694 Link_out
Gene: SLC22A7 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Kobayashi Y, Sakai R, Ohshiro N, Ohbayashi M, Kohyama N, Yamamoto T: Possible involvement of organic anion transporter 2 on the interaction of theophylline with erythromycin in the human liver. Drug Metab Dispos. 2005 May;33(5):619-22. Epub 2005 Feb 11. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on July 26, 2011 08:52

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.