Identification

Summary

Oxtriphylline is a bronchodilator used for the treatment of asthma, bronchitis, COPD, and emphysema.

Brand Names
Choledyl
Generic Name
Oxtriphylline
DrugBank Accession Number
DB01303
Background

Oxtriphylline is the choline salt form of theophylline. Once in the body, theophylline is released and acts as a phosphodiesterase inhibitor, adenosine receptor blocker, and histone deacetylase activator. Its main physiological reponse is to dilate the bronchioles. As such, oxytriphylline is indicated mainly for asthma, bronchospasm, and COPD (i.e. all the same indications as the other theophyllines). It is marketed under the name Choledyl SA, and several forms of oxytriphylline have been discontinued. In the US, oxtriphylline is no longer available.

Type
Small Molecule
Groups
Approved
Structure
Thumb
Weight
Average: 283.3268
Monoisotopic: 283.164439563
Chemical Formula
C12H21N5O3
Synonyms
  • Choline theophyllinate
  • Choline theophylline
  • Cholini theophyllinas
  • Oxtriphylline
  • Teofilinato de colina
  • Theocolin
  • Theophyllinate de choline

Pharmacology

Indication

Used to treat the symptoms of asthma, bronchitis, COPD, and emphysema.

Pharmacology
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Associated Conditions
Contraindications & Blackbox Warnings
Contraindications
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Pharmacodynamics

Oxtriphylline is a bronchodilator. Oxtriphylline works in several ways: it relaxes muscles in your lungs and chest to allow more air in, decreases the sensitivity of your lungs to allergens and other substances that cause inflammation, and increases the contractions of your diaphragm to draw more air into the lungs.

Mechanism of action

Oxtriphylline is a choline salt of theophylline. After ingestion, theophylline is released from oxytriphylline, 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.

TargetActionsOrganism
AcGMP-inhibited 3',5'-cyclic phosphodiesterase A
inhibitor
Humans
AcAMP-specific 3',5'-cyclic phosphodiesterase 4A
inhibitor
Humans
AAdenosine receptor A2a
antagonist
Humans
AAdenosine receptor A1
antagonist
Humans
AHistone deacetylase 2
activator
Humans
Absorption

After ingestion, theophylline is released from oxytriphylline in the acidic environment of the stomach.

Volume of distribution

Theophylline has an apparent volume of distribution of 0.3–0.7 L/kg in children and adults, and the Vd is about twice that of an adult in premature infants.

Protein binding

With a serum concentrations of 17 mcg/mL, adults and children have about 56% theophylline bound to plasma protein, and premature infants have about 36%.

Metabolism

Theophylline undergoes hepatic metabolism to 1,3-dimethyluric acid, 1-methyluric acid, and 3-methylxanthine.

Route of elimination

The kidneys are the main route of elimination for both theophylline and its metabolites, but some unchanged theophylline is eliminated in the feces.

Half-life

The serum half life varies greatly between patients and in age. The half life range for a healthy, nonsmoking adult is 3-12.8 hours, for children is 1.5–9.5 hours, and for for premature infants is 15–58 hours.

Clearance

Theophylline has an average clearance in children (over 6 months) of 1.45 mL/kg per minute, and in healthy, nonsmoking adults of 0.65 mL/kg per hour.

Adverse Effects
Adverseeffects
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Toxicity

Symptoms of toxicity include abdominal pain (continuing or severe), confusion or change in behavior, convulsions (seizures), dark or bloody vomit, diarrhea, dizziness or lightheadedness, fast and/or irregular heartbeat, nervousness or restlessness (continuing), and trembling (continuing).

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
1,2-BenzodiazepineThe therapeutic efficacy of 1,2-Benzodiazepine can be decreased when used in combination with Oxtriphylline.
AbametapirThe serum concentration of Oxtriphylline can be increased when it is combined with Abametapir.
AbataceptThe metabolism of Oxtriphylline can be increased when combined with Abatacept.
AbirateroneThe serum concentration of Oxtriphylline can be increased when it is combined with Abiraterone.
AcebutololThe risk or severity of adverse effects can be increased when Acebutolol is combined with Oxtriphylline.
AcenocoumarolThe metabolism of Acenocoumarol can be decreased when combined with Oxtriphylline.
AcetaminophenThe metabolism of Oxtriphylline can be decreased when combined with Acetaminophen.
AcetazolamideAcetazolamide may increase the excretion rate of Oxtriphylline which could result in a lower serum level and potentially a reduction in efficacy.
AcyclovirThe metabolism of Oxtriphylline can be decreased when combined with Acyclovir.
AdalimumabThe serum concentration of Oxtriphylline can be decreased when it is combined with Adalimumab.
Interactions
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Food Interactions
  • Limit caffeine intake.
  • Take with food. Food reduces irritation.

Products

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International/Other Brands
Choledyl (Warner Chilcott) / Theocolin (Sannova)
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Choledyl Elixir 100mg/5mlElixir100 mg / 5 mLOralErfa Canada 2012 Inc1976-12-31Not applicableCanada flag
Choledyl Pediatric Syr 50mg/5mlSyrup50 mg / 5 mLOralParke Davis Division, Warner Lambert Canada Inc.1981-12-311999-08-13Canada flag
Choledyl Sa Tablets 400mgTablet, extended release400 mgOralErfa Canada 2012 Inc1983-12-312005-07-13Canada flag
Choledyl Sa Tablets 600mgTablet, extended release600 mgOralErfa Canada 2012 Inc1982-12-312005-07-13Canada flag
Choledyl Tab 200mgTablet200 mg / tabOralParke Davis Division, Warner Lambert Canada Inc.1951-12-311999-04-08Canada flag
Oxtriphylline Tab 200mgTablet200 mg / tabOralPro Doc Limitee1983-12-311999-08-12Canada flag
Oxtriphylline Tab 300mgTablet300 mg / tabOralPro Doc Limitee1983-12-311999-08-12Canada flag
Rouphylline Syr 10mg/mlSyrup10 mg / mLOralRougier Pharma Division Of Ratiopharm Inc1975-12-312001-09-05Canada flag
Rouphylline Tab 100mgTablet100 mg / tabOralRougier Pharma Division Of Ratiopharm Inc1980-12-311999-09-27Canada flag
Rouphylline Tab 200mgTablet200 mg / tabOralRougier Pharma Division Of Ratiopharm Inc1980-12-311999-09-27Canada flag
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Apo Oxtriphylline Tab 100mgTablet100 mgOralApotex Corporation1982-12-312019-01-16Canada flag
Apo Oxtriphylline Tab 200mgTablet200 mgOralApotex Corporation1982-12-312019-01-16Canada flag
Apo Oxtriphylline Tab 300mgTablet300 mgOralApotex Corporation1982-12-312019-01-16Canada flag
Novo-triphyl Tab 100mgTablet100 mgOralNovopharm Limited1981-12-312005-08-10Canada flag
Novo-triphyl Tab 200mgTablet200 mgOralNovopharm Limited1981-12-312005-08-10Canada flag
Novo-triphyl Tab 300mgTablet300 mgOralNovopharm Limited1983-12-312005-08-10Canada flag
PMS Oxtriphylline Syr Pediatric 10mg/mlSyrup10 mg / mLOralPharmascience Inc1996-12-312016-10-28Canada flag
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
Choledyl Expectorant ElixirOxtriphylline (100 mg / 5 mL) + Guaifenesin (50 mg / 5 mL)ElixirOralErfa Canada 2012 Inc1981-12-31Not applicableCanada flag
PMS-oxtriphylline ElixirOxtriphylline (20 mg / mL) + Ethanol (.2 mL / mL)ElixirOralPharmascience Inc1992-12-312016-10-28Canada flag
บรองโคดีล ไซรับOxtriphylline (100 MG/5mL) + Guaifenesin (50 MG/5mL)Syrupห้างหุ้นส่วนจำกัด สุพงษ์เภสัช1985-02-22Not applicableThailand flag

Categories

ATC Codes
R03DA20 — Combinations of xanthinesR03DB02 — Choline theophyllinate and adrenergicsR03DA02 — Choline theophyllinate
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as xanthines. These are purine derivatives with a ketone group conjugated at carbons 2 and 6 of the purine moiety.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Imidazopyrimidines
Sub Class
Purines and purine derivatives
Direct Parent
Xanthines
Alternative Parents
6-oxopurines / Alkaloids and derivatives / Pyrimidones / Cholines / Vinylogous amides / Tetraalkylammonium salts / Imidazoles / Heteroaromatic compounds / Ureas / 1,2-aminoalcohols
show 8 more
Substituents
1,2-aminoalcohol / 6-oxopurine / Alcohol / Alkaloid or derivatives / Alkanolamine / Amine / Aromatic heteropolycyclic compound / Azacycle / Azole / Choline
show 21 more
Molecular Framework
Not Available
External Descriptors
Not Available
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
3K045XR58X
CAS number
4499-40-5
InChI Key
RLANKEDHRWMNRO-UHFFFAOYSA-M
InChI
InChI=1S/C7H8N4O2.C5H14NO/c1-10-5-4(8-3-9-5)6(12)11(2)7(10)13;1-6(2,3)4-5-7/h3H,1-2H3,(H,8,9,12);7H,4-5H2,1-3H3/q;+1/p-1
IUPAC Name
(2-hydroxyethyl)trimethylazanium; 1,3-dimethyl-2,6-dioxo-2,3,6,7-tetrahydro-1H-purin-7-ide
SMILES
C[N+](C)(C)CCO.CN1C2=C([N-]C=N2)C(=O)N(C)C1=O

References

Synthesis Reference

Ladenburg, K., Duesel, B.F. and Fand,T.I.; U S . Patent 2,776,287; January 1,1957; assigned to Nepera Chemical Co., Inc.

General References
Not Available
Human Metabolome Database
HMDB0015415
KEGG Drug
D02017
PubChem Compound
656652
PubChem Substance
46507376
ChemSpider
25044543
RxNav
20976
ChEMBL
CHEMBL1200434
Therapeutic Targets Database
DAP000868
PharmGKB
PA164748137
Drugs.com
Drugs.com Drug Page
Wikipedia
Oxtriphylline

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • Warner Chilcott Co. Inc.
Dosage Forms
FormRouteStrength
ElixirOral100 mg / 5 mL
ElixirOral
SyrupOral50 mg / 5 mL
Tablet, extended releaseOral400 mg
Tablet, extended releaseOral600 mg
TabletOral100 mg
TabletOral200 mg
TabletOral300 mg
TabletOral300 mg / tab
SyrupOral10 mg / mL
TabletOral100 mg / tab
TabletOral200 mg / tab
Suppository
Syrup
Prices
Unit descriptionCostUnit
Choledyl 20 mg/ml Elixir0.04USD ml
Pms-Oxtriphylline 20 mg/ml Elixir0.02USD ml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
water solubilitySoluble in alcohol and water.From Lexicomp.
Predicted Properties
PropertyValueSource
Water Solubility3.84 mg/mLALOGPS
logP-0.99ALOGPS
logP-0.77ChemAxon
logS-1.9ALOGPS
pKa (Strongest Acidic)7.82ChemAxon
pKa (Strongest Basic)-0.78ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area66.4 Å2ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity45.51 m3·mol-1ChemAxon
Polarizability16.49 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+0.585
Blood Brain Barrier+0.7679
Caco-2 permeable-0.5861
P-glycoprotein substrateSubstrate0.718
P-glycoprotein inhibitor INon-inhibitor0.9763
P-glycoprotein inhibitor IINon-inhibitor0.9261
Renal organic cation transporterNon-inhibitor0.8496
CYP450 2C9 substrateNon-substrate0.7126
CYP450 2D6 substrateNon-substrate0.8089
CYP450 3A4 substrateSubstrate0.5699
CYP450 1A2 substrateNon-inhibitor0.7873
CYP450 2C9 inhibitorNon-inhibitor0.937
CYP450 2D6 inhibitorNon-inhibitor0.9259
CYP450 2C19 inhibitorNon-inhibitor0.9227
CYP450 3A4 inhibitorNon-inhibitor0.9707
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9716
Ames testNon AMES toxic0.6337
CarcinogenicityNon-carcinogens0.8347
BiodegradationReady biodegradable0.9052
Rat acute toxicity2.5809 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.8706
hERG inhibition (predictor II)Non-inhibitor0.8959
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
Not Available

Targets

Drugtargets2
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insights and accelerate drug research.
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Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Metal ion binding
Specific Function
Cyclic nucleotide phosphodiesterase with a dual-specificity for the second messengers cAMP and cGMP, which are key regulators of many important physiological processes.
Gene Name
PDE3A
Uniprot ID
Q14432
Uniprot Name
cGMP-inhibited 3',5'-cyclic phosphodiesterase A
Molecular Weight
124978.06 Da
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. [Article]
  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. [Article]
  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. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Metal ion binding
Specific Function
Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes.
Gene Name
PDE4A
Uniprot ID
P27815
Uniprot Name
cAMP-specific 3',5'-cyclic phosphodiesterase 4A
Molecular Weight
98142.155 Da
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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Antagonist
General Function
Identical protein binding
Specific Function
Receptor for adenosine. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase.
Gene Name
ADORA2A
Uniprot ID
P29274
Uniprot Name
Adenosine receptor A2a
Molecular Weight
44706.925 Da
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. [Article]
  2. Daly JW, Jacobson KA, Ukena D: Adenosine receptors: development of selective agonists and antagonists. Prog Clin Biol Res. 1987;230:41-63. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Antagonist
General Function
Purine nucleoside binding
Specific Function
Receptor for adenosine. The activity of this receptor is mediated by G proteins which inhibit adenylyl cyclase.
Gene Name
ADORA1
Uniprot ID
P30542
Uniprot Name
Adenosine receptor A1
Molecular Weight
36511.325 Da
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. [Article]
  2. Daly JW, Jacobson KA, Ukena D: Adenosine receptors: development of selective agonists and antagonists. Prog Clin Biol Res. 1987;230:41-63. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Activator
General Function
Transcription factor binding
Specific Function
Responsible for the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4). Histone deacetylation gives a tag for epigenetic repression and plays an impo...
Gene Name
HDAC2
Uniprot ID
Q92769
Uniprot Name
Histone deacetylase 2
Molecular Weight
55363.855 Da
References
  1. Cosio BG, Tsaprouni L, Ito K, Jazrawi E, Adcock IM, Barnes PJ: Theophylline restores histone deacetylase activity and steroid responses in COPD macrophages. J Exp Med. 2004 Sep 6;200(5):689-95. Epub 2004 Aug 30. [Article]
  2. 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. [Article]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
Specific Function
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 un...
Gene Name
CYP1A2
Uniprot ID
P05177
Uniprot Name
Cytochrome P450 1A2
Molecular Weight
58293.76 Da
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. [Article]
  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. [Article]
  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. [Article]
  4. Thorn CF, Aklillu E, Klein TE, Altman RB: PharmGKB summary: very important pharmacogene information for CYP1A2. Pharmacogenet Genomics. 2012 Jan;22(1):73-7. doi: 10.1097/FPC.0b013e32834c6efd. [Article]
  5. Flockhart Table of Drug Interactions [Link]

Transporters

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Mediates sodium-independent multispecific organic anion transport. Transport of prostaglandin E2, prostaglandin F2, tetracycline, bumetanide, estrone sulfate, glutarate, dehydroepiandrosterone sulf...
Gene Name
SLC22A7
Uniprot ID
Q9Y694
Uniprot Name
Solute carrier family 22 member 7
Molecular Weight
60025.025 Da
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. [Article]

Drug created at June 30, 2007 14:28 / Updated at October 26, 2021 21:40