Vonoprazan

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, in combination with amoxicillin and clarithromycin in a co-packaged product, is indicated for the treatment of Helicobacter pylori (H. pylori) infection in adults. Another co-packaged product with only vonoprazan and amoxicillin is also indicated for the treatment of H. pylori infection in adults.5

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Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Treatment ofDuodenal ulcer••••••••••••••••••
Treatment ofErosive esophagitis•••••••••••••••••••••••
Treatment ofGastric ulcer••••••••••••••••••
Prevention ofGastric or duodenal ulcers caused by low-dose aspirin••••••••••••••••••
Symptomatic treatment ofHeartburn•••••••••••••••••••••••
Contraindications & Blackbox Warnings
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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

TargetActionsOrganism
AHydrogen potassium ATPase
inhibitor
Humans
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

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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
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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 Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
Not Available

Interactions

Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
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
AbametapirThe serum concentration of Vonoprazan can be increased when it is combined with Abametapir.
AbataceptThe metabolism of Vonoprazan can be increased when combined with Abatacept.
AbrocitinibThe metabolism of Abrocitinib can be decreased when combined with Vonoprazan.
AcalabrutinibThe metabolism of Vonoprazan can be decreased when combined with Acalabrutinib.
AcenocoumarolThe 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

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Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
VoqueznaTablet26.72 mg/1OralPhathom Pharmaceuticals Inc.2023-11-10Not applicableUS flag
VoqueznaTablet13.36 mg/1OralPhathom Pharmaceuticals Inc.2023-11-10Not applicableUS flag
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
Voquezna Dual PakVonoprazan (26.72 mg/1) + Amoxicillin Trihydrate (500 mg/1)Capsule; Kit; TabletOralPhathom Pharmaceuticals Inc.2023-11-08Not applicableUS flag
Voquezna Triple PakVonoprazan (26.72 mg/1) + Amoxicillin Trihydrate (500 mg/1) + Clarithromycin (500 mg/1)Capsule; Kit; TabletOralPhathom Pharmaceuticals Inc.2023-11-08Not applicableUS flag

Categories

ATC Codes
A02BD14 — Vonoprazan, amoxicillin and clarithromycinA02BD15 — Vonoprazan, amoxicillin and metronidazoleA02BC08 — Vonoprazan
Drug Categories
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
  1. 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]
  2. 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]
  3. 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]
  4. FDA Thailand Product Information: Vocinti (vonoprazan fumarate) oral tablets [Link]
  5. 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]
  6. FDA Approved Drug Products: VOQUEZNA (vonoprazan) tablets, for oral use (November 2023) [Link]
Human Metabolome Database
HMDB0259872
PubChem Compound
15981397
PubChem Substance
347828097
ChemSpider
13112797
BindingDB
394392
RxNav
2604577
ChEBI
136048
ChEMBL
CHEMBL2079130
ZINC
ZINC000034842823
PDBe Ligand
HKT
Wikipedia
Vonoprazan
PDB Entries
5ylu

Clinical Trials

Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
PhaseStatusPurposeConditionsCount
4Active Not RecruitingTreatmentHelicobacter Pylori1
4CompletedTreatmentErosive Esophagitis1
4CompletedTreatmentGastritis Chronic / Helicobacter Pylori Infection1
4CompletedTreatmentHelicobacter Pylori Infection3
4CompletedTreatmentReflux Esophagitis (RE)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
TabletOral10.0000 mg
Tablet, film coatedOral
TabletOral13.36 mg/1
TabletOral26.72 mg/1
Capsule; kit; tabletOral
Tablet, film coatedOral10 mg
Tablet, film coatedOral20 mg
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US9186411No2015-11-172030-08-11US flag
US7977488No2011-07-122028-08-11US flag

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)194.8°CFDA label
water solubilitySlightly solubleFDA label
Predicted Properties
PropertyValueSource
Water Solubility0.049 mg/mLALOGPS
logP1.78ALOGPS
logP2.03Chemaxon
logS-3.8ALOGPS
pKa (Strongest Basic)9.01Chemaxon
Physiological Charge1Chemaxon
Hydrogen Acceptor Count4Chemaxon
Hydrogen Donor Count1Chemaxon
Polar Surface Area63.99 Å2Chemaxon
Rotatable Bond Count4Chemaxon
Refractivity90.16 m3·mol-1Chemaxon
Polarizability34.23 Å3Chemaxon
Number of Rings3Chemaxon
Bioavailability1Chemaxon
Rule of FiveYesChemaxon
Ghose FilterYesChemaxon
Veber's RuleNoChemaxon
MDDR-like RuleNoChemaxon
Predicted ADMET Features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-0002-0009000000-e55f915bc62c7abc4d9c
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-006x-0009000000-9d85bd3e51c28fdc560d
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-0002-0009000000-0d484be6a053a0b41173
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-0006-1009000000-9d9031165c01d3d54ab7
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-00dj-2902000000-0e2ebda92bba9a735ccd
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-01r6-4900000000-0702fd8a5a3bfb49592f
Predicted 1H NMR Spectrum1D NMRNot Applicable
Predicted 13C NMR Spectrum1D NMRNot Applicable
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
[M-H]-175.35698
predicted
DeepCCS 1.0 (2019)
[M+H]+177.94716
predicted
DeepCCS 1.0 (2019)
[M+Na]+185.94215
predicted
DeepCCS 1.0 (2019)

Targets

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Kind
Protein group
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Sodium:potassium-exchanging atpase activity
Specific Function
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.

Components:
References
  1. 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
Vitamin d3 25-hydroxylase activity
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 performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. 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]
  2. 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
Oxygen binding
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
CYP3A5
Uniprot ID
P20815
Uniprot Name
Cytochrome P450 3A5
Molecular Weight
57108.065 Da
References
  1. 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
Steroid hydroxylase activity
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
CYP2B6
Uniprot ID
P20813
Uniprot Name
Cytochrome P450 2B6
Molecular Weight
56277.81 Da
References
  1. 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
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
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 im...
Gene Name
CYP2C19
Uniprot ID
P33261
Uniprot Name
Cytochrome P450 2C19
Molecular Weight
55930.545 Da
References
  1. 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
Steroid hydroxylase activity
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
CYP2C9
Uniprot ID
P11712
Uniprot Name
Cytochrome P450 2C9
Molecular Weight
55627.365 Da
References
  1. 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
Steroid hydroxylase activity
Specific Function
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...
Gene Name
CYP2D6
Uniprot ID
P10635
Uniprot Name
Cytochrome P450 2D6
Molecular Weight
55768.94 Da
References
  1. 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
Toxic substance binding
Specific Function
Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloid...
Gene Name
ALB
Uniprot ID
P02768
Uniprot Name
Serum albumin
Molecular Weight
69365.94 Da
References
  1. 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
Not Available
Specific Function
Functions as 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...
Gene Name
ORM1
Uniprot ID
P02763
Uniprot Name
Alpha-1-acid glycoprotein 1
Molecular Weight
23511.38 Da
References
  1. 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
Xenobiotic-transporting atpase activity
Specific Function
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name
ABCB1
Uniprot ID
P08183
Uniprot Name
Multidrug resistance protein 1
Molecular Weight
141477.255 Da
References
  1. 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 December 12, 2023 05:06