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Identification
NamePantoprazole
Accession NumberDB00213  (APRD00073)
Typesmall molecule
Groupsapproved
Description

Pantoprazole is a proton pump inhibitor drug used for short-term treatment of erosion and ulceration of the esophagus caused by gastroesophageal reflux disease.

Structure
Thumb
Synonyms
SynonymLanguageCode
PantoprazolSpanishINN
PantoprazolumLatinINN
Salts
Name/CAS Structure Properties
Pantoprazole Magnesium
Thumb Not applicable DBSALT000853
Pantoprazole Sodium
138786-67-1
Thumb
  • InChI Key: YNWDKZIIWCEDEE-UHFFFAOYNA-N
  • Monoisotopic Mass: 405.057077726
  • Average Mass: 405.352
DBSALT000386
Brand names
NameCompany
PantolocPfizer
PantozolNot Available
ProtonixNot Available
TectaNycomed
Brand mixturesNot Available
Categories
CAS number102625-70-7
WeightAverage: 383.37
Monoisotopic: 383.075133083
Chemical FormulaC16H15F2N3O4S
InChI KeyInChIKey=IQPSEEYGBUAQFF-UHFFFAOYSA-N
InChI
InChI=1S/C16H15F2N3O4S/c1-23-13-5-6-19-12(14(13)24-2)8-26(22)16-20-10-4-3-9(25-15(17)18)7-11(10)21-16/h3-7,15H,8H2,1-2H3,(H,20,21)
IUPAC Name
6-(difluoromethoxy)-2-{[(3,4-dimethoxypyridin-2-yl)methane]sulfinyl}-1H-1,3-benzodiazole
SMILES
COC1=C(OC)C(CS(=O)C2=NC3=C(N2)C=C(OC(F)F)C=C3)=NC=C1
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassHeterocyclic Compounds
ClassBenzimidazoles
SubclassSulfinylbenzimidazoles
Direct parentSulfinylbenzimidazoles
Alternative parentsPhenol Ethers; Alkyl Aryl Ethers; Pyridines and Derivatives; Imidazoles; Sulfoxides; Polyamines; Alkyl Fluorides; Organofluorides
Substituentsphenol ether; alkyl aryl ether; benzene; pyridine; azole; imidazole; sulfoxide; polyamine; ether; organohalogen; organofluoride; alkyl halide; alkyl fluoride; organonitrogen compound
Classification descriptionThis compound belongs to the sulfinylbenzimidazoles. These are polycyclic aromatic compounds containing a sulfinyl group attached at the position 2 of a benzimidazole moiety.
Pharmacology
IndicationShort-term (up to 16 weeks) treatment of erosive esophagitis.
PharmacodynamicsPantoprazole is a substituted benzimidazole indicated for the short-term treatment (up to 16 weeks) in the healing and symptomatic relief of erosive esophagitis. Pantoprazole is a proton pump inhibitor (PPI) that suppresses the final step in gastric acid production.
Mechanism of actionPantoprazole is a proton pump inhibitor (PPI) that suppresses the final step in gastric acid production by forming a covalent bond to two sites of the (H+,K+ )- ATPase enzyme system at the secretory surface of the gastric parietal cell. This effect is dose- related and leads to inhibition of both basal and stimulated gastric acid secretion irrespective of the stimulus.
AbsorptionPantoprazole is well absorbed. It undergoes little first-pass metabolism resulting in an absolute bioavailability of approximately 77%.
Volume of distribution
  • 11.0 to 23.6 L
Protein binding98%
Metabolism

Pantoprazole is extensively metabolized in the liver through the cytochrome P450 (CYP) system. The main metabolic pathway is demethylation, by CYP2C19, with subsequent sulfation; other metabolic pathways include oxidation by CYP3A4. There is no evidence that any of the pantoprazole metabolites have significant pharmacologic activity.

SubstrateEnzymesProduct
Pantoprazole
    Active Metabolite of PantoprazoleDetails
    Route of eliminationAfter administration of a single intravenous dose of 14C-labeled pantoprazole to healthy, normal metabolizer subjects, approximately 71% of the dose was excreted in the urine with 18% excreted in the feces through biliary excretion.
    Half life1 hour
    Clearance
    • 7.6-14.0 L/h
    ToxicitySingle intravenous doses of pantoprazole at 378, 230, and 266 mg/kg (38, 46, and 177 times the recommended human dose based on body surface area) were lethal to mice, rats and dogs, respectively. The symptoms of toxicity included hypoactivity, ataxia, hunched sitting, limb-splay, lateral position, segregation, absence of ear reflex, and tremor. There is limited experience regarding cases of human overdosage, and treatment should be symptomatic and supportive.
    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 + 0.9935
    Blood Brain Barrier - 0.5777
    Caco-2 permeable + 0.7262
    P-glycoprotein substrate Non-substrate 0.6127
    P-glycoprotein inhibitor I Inhibitor 0.5587
    P-glycoprotein inhibitor II Non-inhibitor 0.9198
    Renal organic cation transporter Non-inhibitor 0.6285
    CYP450 2C9 substrate Non-substrate 0.84
    CYP450 2D6 substrate Non-substrate 0.8683
    CYP450 3A4 substrate Substrate 0.7254
    CYP450 1A2 substrate Inhibitor 0.7639
    CYP450 2C9 substrate Non-inhibitor 0.8054
    CYP450 2D6 substrate Non-inhibitor 0.7308
    CYP450 2C19 substrate Inhibitor 0.7877
    CYP450 3A4 substrate Non-inhibitor 0.7258
    CYP450 inhibitory promiscuity High CYP Inhibitory Promiscuity 0.903
    Ames test Non AMES toxic 0.5527
    Carcinogenicity Non-carcinogens 0.8108
    Biodegradation Not ready biodegradable 0.9972
    Rat acute toxicity 2.3466 LD50, mol/kg Not applicable
    hERG inhibition (predictor I) Weak inhibitor 0.9228
    hERG inhibition (predictor II) Non-inhibitor 0.8734
    Pharmacoeconomics
    Manufacturers
    • Wyeth pharmaceuticals inc
    • Kudco ireland ltd
    • Sun pharma global inc
    • Teva pharmaceuticals usa inc
    Packagers
    Dosage forms
    FormRouteStrength
    Powder, for solutionIntravenous
    Tablet, coatedOral
    Prices
    Unit descriptionCostUnit
    Protonix iv 40 mg vial14.4USDvial
    Protonix 40 mg tablet dr8.91USDtablet
    Protonix 20 mg tablet5.43USDtab
    Protonix 40 mg Enteric Coated Tabs5.43USDtab
    Protonix dr 20 mg tablet5.22USDtablet
    Protonix dr 40 mg tablet5.22USDtablet
    Pantoprazole Sodium 20 mg Enteric Coated Tabs4.26USDtab
    Pantoprazole Sodium 40 mg Enteric Coated Tabs4.26USDtab
    Pantoprazole sod dr 20 mg tablet3.93USDtablet
    Pantoprazole sod dr 40 mg tablet3.93USDtablet
    Pantoloc 40 mg Enteric-Coated Tablet2.28USDtablet
    Apo-Pantoprazole 40 mg Enteric-Coated Tablet1.27USDtablet
    Co Pantoprazole 40 mg Enteric-Coated Tablet1.27USDtablet
    Mylan-Pantoprazole 40 mg Enteric-Coated Tablet1.27USDtablet
    Novo-Pantoprazole 40 mg Enteric-Coated Tablet1.27USDtablet
    Phl-Pantoprazole 40 mg Enteric-Coated Tablet1.27USDtablet
    Pms-Pantoprazole 40 mg Enteric-Coated Tablet1.27USDtablet
    Ran-Pantoprazole 40 mg Enteric-Coated Tablet1.27USDtablet
    Ratio-Pantoprazole 40 mg Enteric-Coated Tablet1.27USDtablet
    Sandoz Pantoprazole 40 mg Enteric-Coated Tablet1.27USDtablet
    DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
    Patents
    CountryPatent NumberApprovedExpires (estimated)
    United States75443702006-12-072026-12-07
    United States47585791993-07-192010-07-19
    Canada24288702006-05-232021-11-17
    Canada20926942005-04-052011-09-06
    Canada23410312006-04-042019-08-12
    Properties
    Statesolid
    Experimental Properties
    PropertyValueSource
    melting pointBecause of gradual degradation of pantoprazole sodium during heating, the melting point cannot be determined.Not Available
    water solubilityFreely soluble in water.Not Available
    logP0.5Not Available
    Predicted Properties
    PropertyValueSource
    water solubility4.95e-01 g/lALOGPS
    logP2.11ALOGPS
    logP2.18ChemAxon
    logS-2.9ALOGPS
    pKa (strongest acidic)9.15ChemAxon
    pKa (strongest basic)3.55ChemAxon
    physiological charge0ChemAxon
    hydrogen acceptor count6ChemAxon
    hydrogen donor count1ChemAxon
    polar surface area86.33ChemAxon
    rotatable bond count7ChemAxon
    refractivity90.05ChemAxon
    polarizability35.17ChemAxon
    number of rings3ChemAxon
    bioavailability1ChemAxon
    rule of fiveYesChemAxon
    Ghose filterYesChemAxon
    Veber's ruleNoChemAxon
    MDDR-like ruleYesChemAxon
    Spectra
    SpectraNot Available
    References
    Synthesis Reference

    Rudolf Linder, “Freeze-dried pantoprazole preparation and pantoprazole injection.” U.S. Patent US20030003058, issued January 02, 2003.

    US20030003058
    General ReferenceNot Available
    External Links
    ResourceLink
    KEGG DrugD05353
    KEGG CompoundC11806
    PubChem Compound4679
    PubChem Substance46504622
    ChemSpider4517
    BindingDB50241342
    ChEBI7915
    ChEMBLCHEMBL1502
    Therapeutic Targets DatabaseDAP000724
    PharmGKBPA450774
    Drug Product Database2241804
    RxListhttp://www.rxlist.com/cgi/generic3/protonix.htm
    Drugs.comhttp://www.drugs.com/cdi/pantoprazole.html
    WikipediaPantoprazole
    ATC CodesA02BC02
    AHFS Codes
    • 56:28.36
    PDB EntriesNot Available
    FDA labelshow(183 KB)
    MSDSshow(58.1 KB)
    Interactions
    Drug Interactions
    Drug
    AtazanavirThis gastric pH modifier decreases the levels/effects of atazanavir
    CefditorenProton pump inhibitors such as pantoprazole may decrease the serum concentration of cefditoren. If possible, avoid use of cefditoren with proton pump inhibitors (PPIs). Consider alternative methods to minimize/control acid reflux (eg, diet modification) or alternative antimicrobial therapy if use of PPIs can not be avoided.
    ClopidogrelPantoprazole may decrease serum concentrations of the active metabolite(s) of clopidogrel. Due to the possible risk for impaired clopidogrel effectiveness with this combination, clinicians should carefully consider the need for concurrent pantoprazole therapy in patients receiving clopidogrel. Monitor response to clopidogrel closely when using clopidogrel with pantoprazole. Whether there are differences among individual proton pump inhibitors is unclear. Other acid-lowering therapies (e.g., H2-receptor antagonists, antacids, etc.) do not appear to share this interaction with clopidogrel.
    Dabigatran etexilateProton pump inhibitors may decrease the bioavailability of dabigatran by 28% and increase inter-patient pharmacokinetic variability, especially in females. However, dose adjustment is not required.
    DabrafenibProton pump inhibitors may alter the solubility of dabrafenib and reduce its bioavailability.
    DasatinibPantoprazole may decrease the serum level of dasatinib.
    EnoxacinPantoprazole may decrease the absorption of enoxacin.
    IndinavirOmeprazole decreases the absorption of indinavir
    ItraconazoleThe proton pump inhibitor, pantoprazole, may decrease the absorption of itraconazole.
    KetoconazoleThe proton pump inhibitor, pantoprazole, may decrease the absorption of ketoconazole.
    RilpivirineProton-pump inhibitors increase gastric pH which causes a decrease in the exposure of rilpivirine thus reducing efficacy.
    TopotecanThe BCRP/ABCG2 inhibitor, Pantaprazole, may increase the bioavailability and serum concentration of oral Topotecan. Monitor for change in the therapeutic and adverse effects of Topotecan if Pantaprazole is initiated, discontinued or dose changed.
    Food Interactions
    • Take without regard to meals.

    1. Potassium-transporting ATPase alpha chain 1

    Kind: protein

    Organism: Human

    Pharmacological action: yes

    Actions: inhibitor

    Components

    Name UniProt ID Details
    Potassium-transporting ATPase alpha chain 1 P20648 Details

    References:

    1. Moreira Dias L: Pantoprazole: a proton pump inhibitor. Clin Drug Investig. 2009;29 Suppl 2:3-12. Pubmed
    2. Cheer SM, Prakash A, Faulds D, Lamb HM: Pantoprazole: an update of its pharmacological properties and therapeutic use in the management of acid-related disorders. Drugs. 2003;63(1):101-33. Pubmed
    3. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

    1. Cytochrome P450 2C19

    Kind: protein

    Organism: Human

    Pharmacological action: unknown

    Actions: substrate inhibitor

    Components

    Name UniProt ID Details
    Cytochrome P450 2C19 P33261 Details

    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. Lexicomp

    2. Cytochrome P450 3A4

    Kind: protein

    Organism: Human

    Pharmacological action: unknown

    Actions: substrate inducer

    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

    3. Cytochrome P450 1A2

    Kind: protein

    Organism: Human

    Pharmacological action: unknown

    Actions: substrate inducer

    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

    4. Cytochrome P450 2C9

    Kind: protein

    Organism: Human

    Pharmacological action: unknown

    Actions: inhibitor

    Components

    Name UniProt ID Details
    Cytochrome P450 2C9 P11712 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

    1. Multidrug resistance protein 1

    Kind: protein

    Organism: Human

    Pharmacological action: unknown

    Actions: inhibitor

    Components

    Name UniProt ID Details
    Multidrug resistance protein 1 P08183 Details

    References:

    1. Pauli-Magnus C, Rekersbrink S, Klotz U, Fromm MF: Interaction of omeprazole, lansoprazole and pantoprazole with P-glycoprotein. Naunyn Schmiedebergs Arch Pharmacol. 2001 Dec;364(6):551-7. Pubmed

    2. ATP-binding cassette sub-family G member 2

    Kind: protein

    Organism: Human

    Pharmacological action: unknown

    Actions: inhibitor

    Components

    Name UniProt ID Details
    ATP-binding cassette sub-family G member 2 Q9UNQ0 Details

    References:

    1. Breedveld P, Zelcer N, Pluim D, Sonmezer O, Tibben MM, Beijnen JH, Schinkel AH, van Tellingen O, Borst P, Schellens JH: Mechanism of the pharmacokinetic interaction between methotrexate and benzimidazoles: potential role for breast cancer resistance protein in clinical drug-drug interactions. Cancer Res. 2004 Aug 15;64(16):5804-11. Pubmed
    2. Suzuki K, Doki K, Homma M, Tamaki H, Hori S, Ohtani H, Sawada Y, Kohda Y: Co-administration of proton pump inhibitors delays elimination of plasma methotrexate in high-dose methotrexate therapy. Br J Clin Pharmacol. 2009 Jan;67(1):44-9. Epub 2008 Nov 17. Pubmed
    3. Dahan A, Amidon GL: Small intestinal efflux mediated by MRP2 and BCRP shifts sulfasalazine intestinal permeability from high to low, enabling its colonic targeting. Am J Physiol Gastrointest Liver Physiol. 2009 Aug;297(2):G371-7. Epub 2009 Jun 18. Pubmed

    3. Solute carrier organic anion transporter family member 1B1

    Kind: protein

    Organism: Human

    Pharmacological action: unknown

    Actions: inhibitor

    Components

    Name UniProt ID Details
    Solute carrier organic anion transporter family member 1B1 Q9Y6L6 Details

    References:

    1. Oostendorp RL, van de Steeg E, van der Kruijssen CM, Beijnen JH, Kenworthy KE, Schinkel AH, Schellens JH: Organic anion-transporting polypeptide 1B1 mediates transport of Gimatecan and BNP1350 and can be inhibited by several classic ATP-binding cassette (ABC) B1 and/or ABCG2 inhibitors. Drug Metab Dispos. 2009 Apr;37(4):917-23. Epub 2009 Jan 12. Pubmed

    Comments
    Drug created on June 13, 2005 07:24 / Updated on September 16, 2013 17:08