Vonoprazan
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Identification
- Summary
Vonoprazan is a potassium-competitive acid blocker used in the treatment of acid-related disorders and as an adjunct to Helicobacter pylori eradication.
- Brand Names
- Voquezna, Voquezna 14 Day Dualpak 20;500, Voquezna 14 Day Triplepak 20;500;500
- Generic Name
- Vonoprazan
- DrugBank Accession Number
- DB11739
- Background
Vonoprazan is a potassium-competitive acid blocker (PCAB) that inhibits H+, K+-ATPase-mediated gastric acid secretion. PCABs represent an alternative to proton-pump inhibitors for the treatment of acid-related disorders. Unlike proton-pump inhibitors, PCABs are not affected by CYP2C19 genetic polymorphisms and do not require acid-resistant formulations.1 Furthermore, vonoprazan is 350-times more potent than the proton-pump inhibitor lansoprazole, thanks to its ability to accumulate in the gastric corpus mucosa, specifically in the parietal cells.2
In February 2015, vonoprazan was first marketed in Japan for the treatment of acid-related disorders and as an adjunct to Helicobacter pylori (H. pylori) eradication.1 In May 2022, the FDA approved the use of vonoprazan in a co-packaged product containing amoxicillin and clarithromycin for the treatment of H. pylori infection.5 Studies have shown that the concomitant use of vonoprazan, amoxicillin, and clarithromycin leads to an H. pylori eradication rate of approximately 90%.3
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Structure
- Weight
- Average: 345.39
Monoisotopic: 345.094726104 - Chemical Formula
- C17H16FN3O2S
- Synonyms
- 1-[5-(2-fluorophenyl)-1-pyridin-3-ylsulfonylpyrrol-3-yl]-N-methylmethanamine
- Vonoprazan
- External IDs
- TAK-438
Pharmacology
- Indication
Vonoprazan is indicated for the following conditions:
- for healing of all grades of erosive esophagitis and relief of heartburn associated with erosive esophagitis in adults.7
- to maintain healing of all grades of erosive esophagitis and relief of heartburn associated with erosive esophagitis in adults.7
- for the relief of heartburn associated with non-erosive gastroesophageal reflux disease in adults.7
- in combination with amoxicillin and clarithromycin for the treatment of Helicobacter pylori (H. pylori) infection in adults.5,7
- in combination with amoxicillin for the treatment of H. pylori infection in adults.7
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Associated Conditions
Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Treatment of Duodenal ulcer •••••••••••• •••••• Treatment of Erosive esophagitis •••••••••••• ••••• •••••• Treatment of Gastric ulcer •••••••••••• •••••• Prevention of Gastric or duodenal ulcers caused by low-dose aspirin •••••••••••• •••••• Symptomatic treatment of Heartburn •••••••••••• ••••• - Contraindications & Blackbox Warnings
- Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API
- Pharmacodynamics
The use of vonoprazan leads to an increase in intragastric pH. The inhibitory effect of vonoprazan on acid secretion increases with repeated daily dosing. Although the antisecretory effect of vonoprazan decreases after drug discontinuation, intragastric pH remains elevated for 24 to 48 hours. Vonoprazan does not have a clinically significant effect on QT prolongation.5
Compared to other potassium-competitive acid blockers (PCABs), vonoprazan has a higher point-positive charge (pKa of 9.06). This allows vonoprazan to accumulate at higher concentrations in the canalicular space of the gastric parietal cells, where it binds H+, K+-ATPase in a K+-competitive and reversible manner. Compared to other PCABs, such as SCH28080, or proton-pump inhibitors, such as lansoprazole, vonoprazan has a more potent H+, K+-ATPase inhibitory activity.1
- Mechanism of action
Vonoprazan is a potassium-competitive acid blocker (PCAB) that inhibits the H+, K+-ATPase enzyme system in a potassium-competitive manner. Through this mechanism, vonoprazan suppresses basal and stimulated gastric acid secretion at the secretory surface of gastric parietal cells.5
Although both classes of drugs inhibit the H+, K+-ATPase, the mechanism of action of PCABs differs from that of proton-pump inhibitors (PPIs). PPIs form a covalent disulphide bond with a cysteine residue on the H+, K+-ATPase, which leads to the inactivation of the enzyme, while PCABs interfere with the binding of K+ to the H+, K+-ATPase.1
Target Actions Organism AHydrogen potassium ATPase inhibitorHumans - Absorption
Vonoprazan has time-independent pharmacokinetics, and steady-state concentrations are reached after 3 to 4 days. In patients given a single dose of vonoprazan, the AUC0-12h, Cmax and Tmax were 154.8 nghr/mL, 25.2 ng/mL, and 2.5 h. In patients given vonoprazan twice daily, the AUC0-12h, Cmax and Tmax were 272.5 nghr/mL, 37.8 ng/mL, and 3.0 h.5 In patients given 10 mg to 40 mg of vonoprazan daily for 7 days, the AUC and Cmax increased in a dose-proportional manner. In healthy subjects given 20 mg of vonoprazan, a high-fat meal led to a 5% and 15% increase in Cmax and AUC; however, these changes were not considered clinically significant.5
- Volume of distribution
Vonoprazan has an apparent oral volume of distribution of 1001 L following a single dose (20 mg). At steady state, the apparent oral volume of distribution of vonoprazan is 782.7 L.5
- Protein binding
In healthy subjects, the plasma protein binding of vonoprazan ranges from 85% to 88%. At plasma concentrations between 0.1 and 10 mcg/mL, the plasma protein binding of vonoprazan is independent of concentration.5
- Metabolism
Vonoprazan is metabolized by several cytochrome P450 (CYP) isoforms, mainly CYP3A4, and to a lesser extent CYP3A5, CYP2B6, CYP2C19, CYP2C9 and CYP2D6. Sulfo- and glucuronosyl-transferases also participate in the metabolism of vonoprazan, and all metabolites are pharmacologically inactive.5,1 CYP3A4 converts vonoprazan into metabolites M-I and M-II, which are then converted to glucuronic-acid-conjugated products M-I-G and M-II-G, respectively.2 Unlike proton pump inhibitors, the presence of CYP2C19 polymorphisms does not have a significant effect on the pharmacokinetics of vonoprazan.5
Hover over products below to view reaction partners
- Route of elimination
Vonoprazan is excreted in urine (67%) and feces (31%). Approximately 8% and 1.4% of the dose administered are recovered unchanged in urine and feces, respectively.5
- Half-life
Vonoprazan has an elimination half-life of 7.1 h following a single dose (20 mg). At steady state, the elimination half-life of vonoprazan is 6.8 h.5
- Clearance
Vonoprazan has an apparent oral clearance of 97.3 L/h following a single dose (20 mg). At steady state, the apparent oral clearance of vonoprazan is 81.3 L/h.5
- Adverse Effects
- Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.
- Toxicity
Overdose with vonoprazan has not been reported. No serious adverse reactions were observed during clinical studies in subjects given a single dose of 120 mg of vonoprazan. Vonoprazan is not removed from the circulation by hemodialysis. In case of overdose, the FDA label for Voquezna Triple Pak and Voquezna Dual Pak recommends symptomatic and supportive treatment.5
Animal studies evaluating vonoprazan mutagenicity (Ames test) have reported negative results. No effects on fertility and reproductive performance were observed in rats given 300 mg/kg/day of vonoprazan orally (133, the maximum recommended human dose). Mice given 6, 20, 60 and 200 mg/kg/day of vonoprazan orally (0.4, 4, 19, and 93 times the maximum recommended human dose) developed hyperplasia of neuroendocrine cells, gastropathy and benign and/or malignant neuroendocrine cell tumors (carcinoids) in the stomach.5
- 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.
Drug Interaction Integrate drug-drug
interactions in your softwareAbametapir The serum concentration of Vonoprazan can be increased when it is combined with Abametapir. Abatacept The metabolism of Vonoprazan can be increased when combined with Abatacept. Abrocitinib The metabolism of Abrocitinib can be decreased when combined with Vonoprazan. Acalabrutinib The metabolism of Vonoprazan can be decreased when combined with Acalabrutinib. Acenocoumarol The metabolism of Acenocoumarol can be decreased when combined with Vonoprazan. - Food Interactions
- Take with or without food. High-fat meals may decrease the absorption of vonoprazan; however, these changes are not considered clinically significant.
Products
- Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Voquezna Tablet 26.72 mg/1 Oral Phathom Pharmaceuticals Inc. 2023-11-10 Not applicable US Voquezna Tablet 13.36 mg/1 Oral Phathom Pharmaceuticals Inc. 2023-11-10 Not applicable US - Mixture Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image Voquezna Dual Pak Vonoprazan (26.72 mg/1) + Amoxicillin Trihydrate (500 mg/1) Capsule; Kit; Tablet Oral Phathom Pharmaceuticals Inc. 2023-11-08 Not applicable US Voquezna Triple Pak Vonoprazan (26.72 mg/1) + Amoxicillin Trihydrate (500 mg/1) + Clarithromycin (500 mg/1) Capsule; Kit; Tablet Oral Phathom Pharmaceuticals Inc. 2023-11-08 Not applicable US
Categories
- ATC Codes
- A02BD14 — Vonoprazan, amoxicillin and clarithromycin
- A02BD — Combinations for eradication of Helicobacter pylori
- A02B — DRUGS FOR PEPTIC ULCER AND GASTRO-OESOPHAGEAL REFLUX DISEASE (GORD)
- A02 — DRUGS FOR ACID RELATED DISORDERS
- A — ALIMENTARY TRACT AND METABOLISM
- A02BD — Combinations for eradication of Helicobacter pylori
- A02B — DRUGS FOR PEPTIC ULCER AND GASTRO-OESOPHAGEAL REFLUX DISEASE (GORD)
- A02 — DRUGS FOR ACID RELATED DISORDERS
- A — ALIMENTARY TRACT AND METABOLISM
- A02BD — Combinations for eradication of Helicobacter pylori
- A02B — DRUGS FOR PEPTIC ULCER AND GASTRO-OESOPHAGEAL REFLUX DISEASE (GORD)
- A02 — DRUGS FOR ACID RELATED DISORDERS
- A — ALIMENTARY TRACT AND METABOLISM
- Drug Categories
- Alimentary Tract and Metabolism
- Amides
- Cytochrome P-450 CYP2B6 Substrates
- Cytochrome P-450 CYP2C19 Inhibitors
- Cytochrome P-450 CYP2C19 inhibitors (strength unknown)
- Cytochrome P-450 CYP2C19 Substrates
- Cytochrome P-450 CYP2C9 Substrates
- Cytochrome P-450 CYP2D6 Substrates
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 CYP3A5 Substrates
- Cytochrome P-450 Enzyme Inhibitors
- Cytochrome P-450 Substrates
- Drugs for Acid Related Disorders
- Drugs for Peptic Ulcer and Gastro-Oesophageal Reflux Disease (Gord)
- Gastric Acid Lowering Agents
- P-glycoprotein inhibitors
- Potassium-competitive Acid Blockers
- Sulfones
- Sulfur Compounds
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as phenylpyrroles. These are polycyclic aromatic compounds containing a benzene ring linked to a pyrrole ring through a CC or CN bond.
- Kingdom
- Organic compounds
- Super Class
- Organoheterocyclic compounds
- Class
- Pyrroles
- Sub Class
- Substituted pyrroles
- Direct Parent
- Phenylpyrroles
- Alternative Parents
- Pyridinesulfonamides / Fluorobenzenes / Aralkylamines / Aryl fluorides / Sulfonyls / Organosulfonic acids and derivatives / Heteroaromatic compounds / Dialkylamines / Azacyclic compounds / Organofluorides show 2 more
- Substituents
- 2-phenylpyrrole / Amine / Aralkylamine / Aromatic heteromonocyclic compound / Aryl fluoride / Aryl halide / Azacycle / Benzenoid / Fluorobenzene / Halobenzene show 17 more
- Molecular Framework
- Aromatic heteromonocyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- 1R5L3J156G
- CAS number
- 881681-00-1
- InChI Key
- BFDBKMOZYNOTPK-UHFFFAOYSA-N
- InChI
- InChI=1S/C17H16FN3O2S/c1-19-10-13-9-17(15-6-2-3-7-16(15)18)21(12-13)24(22,23)14-5-4-8-20-11-14/h2-9,11-12,19H,10H2,1H3
- IUPAC Name
- {[5-(2-fluorophenyl)-1-(pyridine-3-sulfonyl)-1H-pyrrol-3-yl]methyl}(methyl)amine
- SMILES
- CNCC1=CN(C(=C1)C1=CC=CC=C1F)S(=O)(=O)C1=CC=CN=C1
References
- Synthesis Reference
Ikemoto, T., et al. (2016). Process for producing pyrrole compound (U.S. Patent No. US 9,266,831 B2). U.S. Patent and Trademark Office. https://patentimages.storage.googleapis.com/62/60/80/823d4e469ef018/US9266831.pdf
- General References
- Echizen H: The First-in-Class Potassium-Competitive Acid Blocker, Vonoprazan Fumarate: Pharmacokinetic and Pharmacodynamic Considerations. Clin Pharmacokinet. 2016 Apr;55(4):409-18. doi: 10.1007/s40262-015-0326-7. [Article]
- Sugano K: Vonoprazan fumarate, a novel potassium-competitive acid blocker, in the management of gastroesophageal reflux disease: safety and clinical evidence to date. Therap Adv Gastroenterol. 2018 Jan 9;11:1756283X17745776. doi: 10.1177/1756283X17745776. eCollection 2018. [Article]
- Kiyotoki S, Nishikawa J, Sakaida I: Efficacy of Vonoprazan for Helicobacter pylori Eradication. Intern Med. 2020 Jan 15;59(2):153-161. doi: 10.2169/internalmedicine.2521-18. Epub 2019 Jun 27. [Article]
- FDA Thailand Product Information: Vocinti (vonoprazan fumarate) oral tablets [Link]
- FDA Approved Drug Products: VOQUEZNA TRIPLE PAK (vonoprazan tablets; amoxicillin capsules; clarithromycin tablets), co-packaged for oral use and VOQUEZNA DUAL PAK (vonoprazan tablets; amoxicillin capsules) co-packaged for oral use [Link]
- FDA Approved Drug Products: VOQUEZNA (vonoprazan) tablets, for oral use (November 2023) [Link]
- FDA Approved Drug Products: VOQUEZNA (vonoprazan) tablets, for oral use (July 2024) [Link]
- External Links
- Human Metabolome Database
- HMDB0259872
- PubChem Compound
- 15981397
- PubChem Substance
- 347828097
- ChemSpider
- 13112797
- BindingDB
- 394392
- 2604577
- ChEBI
- 136048
- ChEMBL
- CHEMBL2079130
- ZINC
- ZINC000034842823
- PDBe Ligand
- HKT
- Wikipedia
- Vonoprazan
- PDB Entries
- 5ylu
Clinical Trials
- Clinical Trials
Clinical Trial & Rare Diseases Add-on Data Package
Explore 4,000+ rare diseases, orphan drugs & condition pairs, clinical trial why stopped data, & more. Preview package Phase Status Purpose Conditions Count Start Date Why Stopped 100+ additional columns Unlock 175K+ rows when you subscribe.View sample dataNot Available Completed Not Available A History of Gastric or Duodenal Ulcers 1 somestatus stop reason just information to hide Not Available Completed Not Available Gastric or Duodenal Ulcers 1 somestatus stop reason just information to hide Not Available Completed Not Available Gastric Ulcer, Duodenal Ulcer, and Reflux Esophagitis 1 somestatus stop reason just information to hide Not Available Completed Not Available Gastric/Duodenal Ulcer, Gastric MALT Lymphoma, Idiopathic Thrombocytopenic Purpura, or H. Pylori Gastritis, and Other 1 somestatus stop reason just information to hide Not Available Completed Not Available Helicobacter Pylori 1 somestatus stop reason just information to hide
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Tablet Oral 10.0000 mg Tablet, film coated Oral Tablet Oral 13.36 mg/1 Tablet Oral 26.72 mg/1 Capsule; kit; tablet Oral Tablet, film coated Oral 10 mg Tablet, film coated Oral 20 mg - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US9186411 No 2015-11-17 2030-08-11 US US7977488 No 2011-07-12 2028-08-11 US
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 194.8°C FDA label water solubility Slightly soluble FDA label - Predicted Properties
Property Value Source Water Solubility 0.049 mg/mL ALOGPS logP 1.78 ALOGPS logP 2.03 Chemaxon logS -3.8 ALOGPS pKa (Strongest Basic) 9.01 Chemaxon Physiological Charge 1 Chemaxon Hydrogen Acceptor Count 4 Chemaxon Hydrogen Donor Count 1 Chemaxon Polar Surface Area 63.99 Å2 Chemaxon Rotatable Bond Count 4 Chemaxon Refractivity 90.16 m3·mol-1 Chemaxon Polarizability 34.23 Å3 Chemaxon Number of Rings 3 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS splash10-0002-0009000000-e55f915bc62c7abc4d9c Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-006x-0009000000-9d85bd3e51c28fdc560d Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-0002-0009000000-0d484be6a053a0b41173 Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-0006-1009000000-9d9031165c01d3d54ab7 Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-00dj-2902000000-0e2ebda92bba9a735ccd Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-01r6-4900000000-0702fd8a5a3bfb49592f Predicted 1H NMR Spectrum 1D NMR Not Applicable Predicted 13C NMR Spectrum 1D NMR Not Applicable - Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 175.35698 predictedDeepCCS 1.0 (2019) [M+H]+ 177.94716 predictedDeepCCS 1.0 (2019) [M+Na]+ 185.94215 predictedDeepCCS 1.0 (2019)
Targets
- Kind
- Protein group
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- The catalytic subunit of the gastric H(+)/K(+) ATPase pump which transports H(+) ions in exchange for K(+) ions across the apical membrane of parietal cells. Uses ATP as an energy source to pump H(+) ions to the gastric lumen while transporting K(+) ion from the lumen into the cell (By similarity). Remarkably generates a million-fold proton gradient across the gastric parietal cell membrane, acidifying the gastric juice down to pH 1 (By similarity). Within a transport cycle, the transfer of a H(+) ion across the membrane is coupled to ATP hydrolysis and is associated with a transient phosphorylation that shifts the pump conformation from inward-facing (E1) to outward-facing state (E2). The release of the H(+) ion in the stomach lumen is followed by binding of K(+) ion converting the pump conformation back to the E1 state (By similarity)
- Specific Function
- ATP binding
Components:
Name | UniProt ID |
---|---|
Potassium-transporting ATPase alpha chain 1 | P20648 |
Potassium-transporting ATPase subunit beta | P51164 |
References
- FDA Approved Drug Products: VOQUEZNA TRIPLE PAK (vonoprazan tablets; amoxicillin capsules; clarithromycin tablets), co-packaged for oral use and VOQUEZNA DUAL PAK (vonoprazan tablets; amoxicillin capsules) co-packaged for oral use [Link]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of sterols, steroid hormones, retinoids and fatty acids (PubMed:10681376, PubMed:11093772, PubMed:11555828, PubMed:12865317, PubMed:14559847, PubMed:15373842, PubMed:15764715, PubMed:19965576, PubMed:20702771, PubMed:21490593, PubMed:21576599). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase). Catalyzes the hydroxylation of carbon-hydrogen bonds (PubMed:12865317, PubMed:14559847, PubMed:15373842, PubMed:15764715, PubMed:21490593, PubMed:21576599, PubMed:2732228). Exhibits high catalytic activity for the formation of hydroxyestrogens from estrone (E1) and 17beta-estradiol (E2), namely 2-hydroxy E1 and E2, as well as D-ring hydroxylated E1 and E2 at the C-16 position (PubMed:11555828, PubMed:12865317, PubMed:14559847). Plays a role in the metabolism of androgens, particularly in oxidative deactivation of testosterone (PubMed:15373842, PubMed:15764715, PubMed:22773874, PubMed:2732228). Metabolizes testosterone to less biologically active 2beta- and 6beta-hydroxytestosterones (PubMed:15373842, PubMed:15764715, PubMed:2732228). Contributes to the formation of hydroxycholesterols (oxysterols), particularly A-ring hydroxylated cholesterol at the C-4beta position, and side chain hydroxylated cholesterol at the C-25 position, likely contributing to cholesterol degradation and bile acid biosynthesis (PubMed:21576599). Catalyzes bisallylic hydroxylation of polyunsaturated fatty acids (PUFA) (PubMed:9435160). Catalyzes the epoxidation of double bonds of PUFA with a preference for the last double bond (PubMed:19965576). Metabolizes endocannabinoid arachidonoylethanolamide (anandamide) to 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid ethanolamides (EpETrE-EAs), potentially modulating endocannabinoid system signaling (PubMed:20702771). Plays a role in the metabolism of retinoids. Displays high catalytic activity for oxidation of all-trans-retinol to all-trans-retinal, a rate-limiting step for the biosynthesis of all-trans-retinoic acid (atRA) (PubMed:10681376). Further metabolizes atRA toward 4-hydroxyretinoate and may play a role in hepatic atRA clearance (PubMed:11093772). Responsible for oxidative metabolism of xenobiotics. Acts as a 2-exo-monooxygenase for plant lipid 1,8-cineole (eucalyptol) (PubMed:11159812). Metabolizes the majority of the administered drugs. Catalyzes sulfoxidation of the anthelmintics albendazole and fenbendazole (PubMed:10759686). Hydroxylates antimalarial drug quinine (PubMed:8968357). Acts as a 1,4-cineole 2-exo-monooxygenase (PubMed:11695850). Also involved in vitamin D catabolism and calcium homeostasis. Catalyzes the inactivation of the active hormone calcitriol (1-alpha,25-dihydroxyvitamin D(3)) (PubMed:29461981)
- Specific Function
- 1,8-cineole 2-exo-monooxygenase activity
- Gene Name
- CYP3A4
- Uniprot ID
- P08684
- Uniprot Name
- Cytochrome P450 3A4
- Molecular Weight
- 57342.67 Da
References
- Echizen H: The First-in-Class Potassium-Competitive Acid Blocker, Vonoprazan Fumarate: Pharmacokinetic and Pharmacodynamic Considerations. Clin Pharmacokinet. 2016 Apr;55(4):409-18. doi: 10.1007/s40262-015-0326-7. [Article]
- FDA Approved Drug Products: VOQUEZNA TRIPLE PAK (vonoprazan tablets; amoxicillin capsules; clarithromycin tablets), co-packaged for oral use and VOQUEZNA DUAL PAK (vonoprazan tablets; amoxicillin capsules) co-packaged for oral use [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of steroid hormones and vitamins (PubMed:10681376, PubMed:11093772, PubMed:12865317, PubMed:2732228). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase). Catalyzes the hydroxylation of carbon-hydrogen bonds (PubMed:10681376, PubMed:11093772, PubMed:12865317, PubMed:2732228). Exhibits high catalytic activity for the formation of catechol estrogens from 17beta-estradiol (E2) and estrone (E1), namely 2-hydroxy E1 and E2 (PubMed:12865317). Catalyzes 6beta-hydroxylation of the steroid hormones testosterone, progesterone, and androstenedione (PubMed:2732228). Catalyzes the oxidative conversion of all-trans-retinol to all-trans-retinal, a rate-limiting step for the biosynthesis of all-trans-retinoic acid (atRA) (PubMed:10681376). Further metabolizes all trans-retinoic acid (atRA) to 4-hydroxyretinoate and may play a role in hepatic atRA clearance (PubMed:11093772). Also involved in the oxidative metabolism of xenobiotics, including calcium channel blocking drug nifedipine and immunosuppressive drug cyclosporine (PubMed:2732228)
- Specific Function
- aromatase activity
- Gene Name
- CYP3A5
- Uniprot ID
- P20815
- Uniprot Name
- Cytochrome P450 3A5
- Molecular Weight
- 57108.065 Da
References
- FDA Approved Drug Products: VOQUEZNA TRIPLE PAK (vonoprazan tablets; amoxicillin capsules; clarithromycin tablets), co-packaged for oral use and VOQUEZNA DUAL PAK (vonoprazan tablets; amoxicillin capsules) co-packaged for oral use [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of endocannabinoids and steroids (PubMed:12865317, PubMed:21289075). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase). Catalyzes the epoxidation of double bonds of arachidonoylethanolamide (anandamide) to 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid ethanolamides (EpETrE-EAs), potentially modulating endocannabinoid system signaling (PubMed:21289075). Hydroxylates steroid hormones, including testosterone at C-16 and estrogens at C-2 (PubMed:12865317, PubMed:21289075). Plays a role in the oxidative metabolism of xenobiotics, including plant lipids and drugs (PubMed:11695850, PubMed:22909231). Acts as a 1,4-cineole 2-exo-monooxygenase (PubMed:11695850)
- Specific Function
- anandamide 11,12 epoxidase activity
- Gene Name
- CYP2B6
- Uniprot ID
- P20813
- Uniprot Name
- Cytochrome P450 2B6
- Molecular Weight
- 56277.81 Da
References
- FDA Approved Drug Products: VOQUEZNA TRIPLE PAK (vonoprazan tablets; amoxicillin capsules; clarithromycin tablets), co-packaged for oral use and VOQUEZNA DUAL PAK (vonoprazan tablets; amoxicillin capsules) co-packaged for oral use [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- SubstrateInhibitor
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of polyunsaturated fatty acids (PUFA) (PubMed:18577768, PubMed:19965576, PubMed:20972997). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:18577768, PubMed:19965576, PubMed:20972997). Catalyzes the hydroxylation of carbon-hydrogen bonds. Hydroxylates PUFA specifically at the omega-1 position (PubMed:18577768). Catalyzes the epoxidation of double bonds of PUFA (PubMed:19965576, PubMed:20972997). Also metabolizes plant monoterpenes such as limonene. Oxygenates (R)- and (S)-limonene to produce carveol and perillyl alcohol (PubMed:11950794). 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. Hydroxylates fenbendazole at the 4' position (PubMed:23959307)
- Specific Function
- (R)-limonene 6-monooxygenase activity
- Gene Name
- CYP2C19
- Uniprot ID
- P33261
- Uniprot Name
- Cytochrome P450 2C19
- Molecular Weight
- 55944.565 Da
References
- FDA Approved Drug Products: VOQUEZNA TRIPLE PAK (vonoprazan tablets; amoxicillin capsules; clarithromycin tablets), co-packaged for oral use and VOQUEZNA DUAL PAK (vonoprazan tablets; amoxicillin capsules) co-packaged for oral use [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of various endogenous substrates, including fatty acids and steroids (PubMed:12865317, PubMed:15766564, PubMed:19965576, PubMed:21576599, PubMed:7574697, PubMed:9435160, PubMed:9866708). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:12865317, PubMed:15766564, PubMed:19965576, PubMed:21576599, PubMed:7574697, PubMed:9435160, PubMed:9866708). Catalyzes the epoxidation of double bonds of polyunsaturated fatty acids (PUFA) (PubMed:15766564, PubMed:19965576, PubMed:7574697, PubMed:9866708). Catalyzes the hydroxylation of carbon-hydrogen bonds. Metabolizes cholesterol toward 25-hydroxycholesterol, a physiological regulator of cellular cholesterol homeostasis (PubMed:21576599). Exhibits low catalytic activity for the formation of catechol estrogens from 17beta-estradiol (E2) and estrone (E1), namely 2-hydroxy E1 and E2 (PubMed:12865317). Catalyzes bisallylic hydroxylation and hydroxylation with double-bond migration of polyunsaturated fatty acids (PUFA) (PubMed:9435160, PubMed:9866708). Also metabolizes plant monoterpenes such as limonene. Oxygenates (R)- and (S)-limonene to produce carveol and perillyl alcohol (PubMed:11950794). Contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S-warfarin, diclofenac, phenytoin, tolbutamide and losartan (PubMed:25994031)
- Specific Function
- (R)-limonene 6-monooxygenase activity
- Gene Name
- CYP2C9
- Uniprot ID
- P11712
- Uniprot Name
- Cytochrome P450 2C9
- Molecular Weight
- 55627.365 Da
References
- FDA Approved Drug Products: VOQUEZNA TRIPLE PAK (vonoprazan tablets; amoxicillin capsules; clarithromycin tablets), co-packaged for oral use and VOQUEZNA DUAL PAK (vonoprazan tablets; amoxicillin capsules) co-packaged for oral use [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of fatty acids, steroids and retinoids (PubMed:18698000, PubMed:19965576, PubMed:20972997, PubMed:21289075, PubMed:21576599). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:18698000, PubMed:19965576, PubMed:20972997, PubMed:21289075, PubMed:21576599). Catalyzes the epoxidation of double bonds of polyunsaturated fatty acids (PUFA) (PubMed:19965576, PubMed:20972997). Metabolizes endocannabinoid arachidonoylethanolamide (anandamide) to 20-hydroxyeicosatetraenoic acid ethanolamide (20-HETE-EA) and 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid ethanolamides (EpETrE-EAs), potentially modulating endocannabinoid system signaling (PubMed:18698000, PubMed:21289075). Catalyzes the hydroxylation of carbon-hydrogen bonds. Metabolizes cholesterol toward 25-hydroxycholesterol, a physiological regulator of cellular cholesterol homeostasis (PubMed:21576599). Catalyzes the oxidative transformations of all-trans retinol to all-trans retinal, a precursor for the active form all-trans-retinoic acid (PubMed:10681376). Also involved in the oxidative metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants
- Specific Function
- anandamide 11,12 epoxidase activity
- Gene Name
- CYP2D6
- Uniprot ID
- P10635
- Uniprot Name
- Cytochrome P450 2D6
- Molecular Weight
- 55768.94 Da
References
- FDA Approved Drug Products: VOQUEZNA TRIPLE PAK (vonoprazan tablets; amoxicillin capsules; clarithromycin tablets), co-packaged for oral use and VOQUEZNA DUAL PAK (vonoprazan tablets; amoxicillin capsules) co-packaged for oral use [Link]
Carriers
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Binder
- General Function
- Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transporter in plasma, typically binds about 80% of all plasma zinc (PubMed:19021548). Major calcium and magnesium transporter in plasma, binds approximately 45% of circulating calcium and magnesium in plasma (By similarity). Potentially has more than two calcium-binding sites and might additionally bind calcium in a non-specific manner (By similarity). The shared binding site between zinc and calcium at residue Asp-273 suggests a crosstalk between zinc and calcium transport in the blood (By similarity). The rank order of affinity is zinc > calcium > magnesium (By similarity). Binds to the bacterial siderophore enterobactin and inhibits enterobactin-mediated iron uptake of E.coli from ferric transferrin, and may thereby limit the utilization of iron and growth of enteric bacteria such as E.coli (PubMed:6234017). Does not prevent iron uptake by the bacterial siderophore aerobactin (PubMed:6234017)
- Specific Function
- antioxidant activity
- Gene Name
- ALB
- Uniprot ID
- P02768
- Uniprot Name
- Albumin
- Molecular Weight
- 69365.94 Da
References
- Echizen H: The First-in-Class Potassium-Competitive Acid Blocker, Vonoprazan Fumarate: Pharmacokinetic and Pharmacodynamic Considerations. Clin Pharmacokinet. 2016 Apr;55(4):409-18. doi: 10.1007/s40262-015-0326-7. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Binder
- General Function
- Functions as a transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in the body. Appears to function in modulating the activity of the immune system during the acute-phase reaction
- Specific Function
- Not Available
- Gene Name
- ORM1
- Uniprot ID
- P02763
- Uniprot Name
- Alpha-1-acid glycoprotein 1
- Molecular Weight
- 23539.43 Da
References
- Echizen H: The First-in-Class Potassium-Competitive Acid Blocker, Vonoprazan Fumarate: Pharmacokinetic and Pharmacodynamic Considerations. Clin Pharmacokinet. 2016 Apr;55(4):409-18. doi: 10.1007/s40262-015-0326-7. [Article]
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Translocates drugs and phospholipids across the membrane (PubMed:2897240, PubMed:35970996, PubMed:8898203, PubMed:9038218). Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of phosphatidylcholine, phosphatidylethanolamine, beta-D-glucosylceramides and sphingomyelins (PubMed:8898203). Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells (PubMed:2897240, PubMed:35970996, PubMed:9038218)
- Specific Function
- ABC-type xenobiotic transporter activity
- Gene Name
- ABCB1
- Uniprot ID
- P08183
- Uniprot Name
- ATP-dependent translocase ABCB1
- Molecular Weight
- 141477.255 Da
References
- Echizen H: The First-in-Class Potassium-Competitive Acid Blocker, Vonoprazan Fumarate: Pharmacokinetic and Pharmacodynamic Considerations. Clin Pharmacokinet. 2016 Apr;55(4):409-18. doi: 10.1007/s40262-015-0326-7. [Article]
Drug created at October 20, 2016 20:43 / Updated at October 29, 2024 18:06