Banner
Identification
Name Pantoprazole
Accession Number DB00213 (APRD00073)
Type small molecule
Groups approved
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
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
  • Pantoprazol [INN-Spanish]
  • Pantoprazole Na
  • Pantoprazole Sodium
  • Pantoprazolum [INN-Latin]
  • Pantoprozole
Brand names
  • Astropan
  • Pantoloc
  • Pantopan
  • Pantor
  • Pantozol
  • Protium
  • Protonix
  • Protonix I.V.
  • Protonix IV
Brand name mixtures Not Available
Categories
  • Anti-Ulcer Agents
  • Proton-pump Inhibitors
CAS number 102625-70-7
Weight Average: 383.37
Monoisotopic: 383.075133083
Chemical Formula C16H15F2N3O4S
InChI Key InChIKey=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)
Plain Text
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
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Phenols and Derivatives
  • Benzimidazoles
  • Ethers
  • Anisoles
Substructures
  • Carboxylic Acids and Derivatives
  • Phenols and Derivatives
  • Benzimidazoles
  • Pyridines and Derivatives
  • Ethers
  • Halogen Derivatives
  • Benzene and Derivatives
  • Imidazoles
  • Heterocyclic compounds
  • Aromatic compounds
  • Anisoles
  • Imines
  • Cyanamides
  • Phenyl Esters
  • Sulfoxides
Pharmacology
Indication Short-term (up to 16 weeks) treatment of erosive esophagitis.
Pharmacodynamics Pantoprazole 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 action Pantoprazole 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.
Absorption Pantoprazole 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 binding 98%
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.
Route of elimination After 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 life 1 hour
Clearance
  • 7.6-14.0 L/h
Toxicity Single 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
Pathways
Pathway Name SMPDB ID
Smp00228 Pantoprazole Pathway SMP00228
Pharmacoeconomics
Manufacturers
  • Wyeth pharmaceuticals inc
  • Kudco ireland ltd
  • Sun pharma global inc
  • Teva pharmaceuticals usa inc
Packagers
Dosage forms
Form Route Strength
Powder, for solution Intravenous
Tablet, coated Oral
Prices
Unit description Cost Unit
Protonix iv 40 mg vial 14.4 USD vial
Protonix 40 mg tablet dr 8.91 USD tablet
Protonix 20 mg tablet 5.43 USD tab
Protonix 40 mg Enteric Coated Tabs 5.43 USD tab
Protonix dr 20 mg tablet 5.22 USD tablet
Protonix dr 40 mg tablet 5.22 USD tablet
Pantoprazole Sodium 20 mg Enteric Coated Tabs 4.26 USD tab
Pantoprazole Sodium 40 mg Enteric Coated Tabs 4.26 USD tab
Pantoprazole sod dr 20 mg tablet 3.93 USD tablet
Pantoprazole sod dr 40 mg tablet 3.93 USD tablet
Pantoloc 40 mg Enteric-Coated Tablet 2.28 USD tablet
Apo-Pantoprazole 40 mg Enteric-Coated Tablet 1.27 USD tablet
Co Pantoprazole 40 mg Enteric-Coated Tablet 1.27 USD tablet
Mylan-Pantoprazole 40 mg Enteric-Coated Tablet 1.27 USD tablet
Novo-Pantoprazole 40 mg Enteric-Coated Tablet 1.27 USD tablet
Phl-Pantoprazole 40 mg Enteric-Coated Tablet 1.27 USD tablet
Pms-Pantoprazole 40 mg Enteric-Coated Tablet 1.27 USD tablet
Ran-Pantoprazole 40 mg Enteric-Coated Tablet 1.27 USD tablet
Ratio-Pantoprazole 40 mg Enteric-Coated Tablet 1.27 USD tablet
Sandoz Pantoprazole 40 mg Enteric-Coated Tablet 1.27 USD tablet
Patents
Country Patent Number Approved Expires
United States 7544370 2006-12-07 2026-12-07
United States 4758579 1993-07-19 2010-07-19
Canada 2428870 2006-05-23 2021-11-17
Canada 2092694 2005-04-05 2011-09-06
Canada 2341031 2006-04-04 2019-08-12
Properties
State solid
Melting point Because of gradual degradation of pantoprazole sodium during heating, the melting point cannot be determined.
Experimental Properties
Property Value Source
water solubility Freely soluble in water. PhysProp
logP 0.5 PhysProp
Predicted Properties
Property Value Source
water solubility 4.95e-01 g/l ALOGPS
logP 2.11 ALOGPS
logP 2.18 ChemAxon Molconvert
logS -2.89 ALOGPS
pKa 15.76 ChemAxon Molconvert
hydrogen acceptor count 6 ChemAxon Molconvert
hydrogen donor count 1 ChemAxon Molconvert
polar surface area 86.33 ChemAxon Molconvert
rotatable bond count 7 ChemAxon Molconvert
refractivity 90.05 ChemAxon Molconvert
polarizability 35.17 ChemAxon Molconvert
References
Synthesis Reference Not Available
General Reference Not Available
External Links
Resource Link
KEGG Drug D05353 Link_out
KEGG Compound C11806 Link_out
PubChem Compound 4679 Link_out
PubChem Substance 46504622 Link_out
ChemSpider 4517 Link_out
BindingDB 50241342 Link_out
ChEBI 7915 Link_out
ChEMBL 7915 Link_out
Therapeutic Targets Database DAP000724 Link_out
PharmGKB PA450774 Link_out
Drug Product Database 2241804 Link_out
RxList http://www.rxlist.com/cgi/generic3/protonix.htm Link_out
Drugs.com http://www.drugs.com/cdi/pantoprazole.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Pantoprazole Link_out
ATC Codes
  • A02BC02
AHFS Codes
  • 56:28.36
PDB Entries Not Available
FDA label show (183.2 KB)
MSDS show (58.1 KB)
Interactions
Drug Interactions Not Available
Food Interactions
  • Take without regard to meals.
Targets

1. Potassium-transporting ATPase alpha chain 1

Pharmacological action: yes
Actions: inhibitor

Catalyzes the hydrolysis of ATP coupled with the exchange of H(+) and K(+) ions across the plasma membrane. Responsible for acid production in the stomach

Organism class: human
UniProt ID: P20648 Link_out
Gene: ATP4A Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
Enzymes

1. Cytochrome P450 2C19

Actions: substrate, inhibitor

Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and imipramine

UniProt ID: P33261 Link_out
Gene: CYP2C19 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

2. Cytochrome P450 3A4

Actions: substrate, inducer

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

3. Cytochrome P450 1A2

Actions: substrate, inducer

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. 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

Actions: 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. 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
Transporters

1. Multidrug resistance protein 1

Actions: inhibitor

Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells

UniProt ID: P08183 Link_out
Gene: ABCB1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Actions: inhibitor

Xenobiotic transporter that may play an important role in the exclusion of xenobiotics from the brain. May be involved in brain-to-blood efflux. Appears to play a major role in the multidrug resistance phenotype of several cancer cell lines. When overexpressed, the transfected cells become resistant to mitoxantrone, daunorubicin and doxorubicin, display diminished intracellular accumulation of daunorubicin, and manifest an ATP- dependent increase in the efflux of rhodamine 123

UniProt ID: Q9UNQ0 Link_out
Gene: ABCG2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Actions: inhibitor

Mediates the Na(+)-independent transport of organic anions such as pravastatin, taurocholate, methotrexate, dehydroepiandrosterone sulfate, 17-beta-glucuronosyl estradiol, estrone sulfate, prostaglandin E2, thromboxane B2, leukotriene C3, leukotriene E4, thyroxine and triiodothyronine. May play an important role in the clearance of bile acids and organic anions from the liver

UniProt ID: Q9Y6L6 Link_out
Gene: SLCO1B1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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 April 19, 2011 15:02

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.