Identification
- Summary
Pibrentasvir is a Hepatitis C NS5A inhibitor used to treat Hepatitis C.
- Brand Names
- Maviret, Mavyret
- Generic Name
- Pibrentasvir
- DrugBank Accession Number
- DB13878
- Background
Pibrentasvir is a direct acting antiviral agent and Hepatitis C virus (HCV) NS5A inhibitor that targets the the viral RNA replication and viron assembly. In combination with Glecaprevir, pibrentastiv is a useful therapy for patients who experienced therapeutic failure from other NS5A inhibitors. In cell cultures, the emergence of amino acid substitutions at known NS5A inhibitor resistance-associated positions in HCV genotype 1a, 2a or 3a replicons led to reduced susceptibility and resistance to pibrentasvir Label. These resistance-associated amino acid substitutions included Q30D/deletion, Y93D/H/N or H58D +Y93H in genotype 1a replicons, F28S + M31I or P29S + K30G in genotype 2a replicons, and Y93H in genotype 3a replicons. Individual NS5A amino acid substitutions that reduced susceptibility to pibrentasvir include M28G or Q30D in a genotype 1a replicon and P32-deletion in a genotype 1b replicon Label.
Pibrentasvir is available as an oral combination therapy with Glecaprevir under the brand name Mavyret. This fixed-dose combination therapy was FDA-approved in August 2017 to treat adults with chronic hepatitis C virus (HCV) genotypes 1-6 without cirrhosis (liver disease) or with mild cirrhosis, including patients with moderate to severe kidney disease and those who are on dialysis 3. Mavyret is also indicated for HCV genotype 1-infected patients who have been previously treated with regimens either containing an NS5A inhibitor or an NS3/4A protease inhibitor, but not both 3. Hepatitis C viral infection often leads to decreased liver function and subsequent liver failure, causing a significantly negative impact on the patients' quality of life. The ultimate goal of the combination treatment is to achieve sustained virologic response (SVR) and cure the patients from the infection. In clinical trials, this combination therapy achieved SVR12 rate, or undetectable Hepatitis C for twelve or more weeks after the end of treatment, of ≥93% across genotypes 1a, 2a, 3a, 4, 5 and 6 Label.
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Structure
Structure for Pibrentasvir (DB13878)
- Weight
- Average: 1113.201
Monoisotopic: 1112.490699908 - Chemical Formula
- C57H65F5N10O8
- Synonyms
- Pibrentasvir
- External IDs
- A-1325912.0
- ABT 530
- ABT-530
Pharmacology
- Indication
Indicated for the treatment of adult patients with chronic hepatitis C virus (HCV) genotype 1, 2, 3, 4, 5 or 6 infection without cirrhosis or with compensated cirrhosis (Child-Pugh A). MAVYRET is also indicated for the treatment of adult patients with HCV genotype 1 infection, who previously have been treated with a regimen containing an HCV NS5A inhibitor or an NS3/4A protease inhibitor (PI), but not both Label.
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 Used in combination to treat Chronic hepatitis c genotype 1 Combination Product in combination with: Glecaprevir (DB13879) •••••••••••• ••••••••••• ••••• ••••••• Used in combination to treat Chronic hepatitis c genotype 1 Combination Product in combination with: Glecaprevir (DB13879) •••••••••••• Used in combination to treat Chronic hepatitis c genotype 1 Combination Product in combination with: Glecaprevir (DB13879) •••••••••••• •••••••• ••••••••• •••• •••• ••••••••• Used in combination to treat Chronic hepatitis c genotype 1 Combination Product in combination with: Glecaprevir (DB13879) •••••••••••• •••••••• ••••••••• •••• •••••• •••••••• ••••••••• Used in combination to treat Chronic hepatitis c virus (hcv) infection Combination Product in combination with: Glecaprevir (DB13879) •••••••••••• •••••• ••••••••• •••• •••••• •• •• ••••• •• •• •••••••• •••••• - Contraindications & Blackbox Warnings
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Pibrentasvir is a pan-genotypic . According to HCV replicon assays, pibrentasvir has EC50 values ranging from 0.08-4.6 nM agaisnt laboratory and clinical isolates from subtypes 1a, 1b, 2a, 2b, 3a, 4a, 4d, 5a, and 6a, or EC50 values of 0.5-4.3 pM against laboratory and clinical isolates from subtypes 1a, 1b, 2a, 2b, 3a, 4a, 4b, 4d, 5a, 6a, 6e and 6p Label. It is active against common resistance-conferring substitutions in HCV genotypes 1 to 6 that confers resistance and decreased therapeutic response from other NS5A inhibitors, inluding positions 24, 28, 30, 31, 58, 92, or 93 in NS5A Label,1. In a QT study, pibrentasvir is not shown to prolong the QTc interval.
- Mechanism of action
NS5A is a phosphoprotein that plays an essential role in replication, assembly and maturation of infectious viral proteins. The basal phosphorylated form of NS5A, which is maintained by C-terminal serine cluster, is key in ensuring its interaction with the viral capsid protein, or the core protein. By blocking this interaction, pibrentasvir inhibits the assembly of proteins and production of mature HCV particles 2. NS5A also interacts with viral and cellular proteins to form the HCV replicase complex, and supports the RNA replication of HCV 1.
Target Actions Organism ANonstructural protein 5A inhibitorHepatitis C Virus - Absorption
In healthy subjects, the time it takes to reach the peak plasma concentration (Tmax) is approximately 5 hours. The mean peak plasma concentration (Cmax) is 110ng/mL in non-cirrhotic HCV-infected subjects. Relative to fasting conditions, the consumption of meals increases the absorption of pibrentasvir by 40-53% Label.
- Volume of distribution
Not Available
- Protein binding
Pibrentasvir is >99.9% bound to human plasma proteins. The Blood-to-plasma ratio is approximately 0.62 Label.
- Metabolism
Pibrentasvir is not metabolized Label.
- Route of elimination
The predominant route of elimination of the drug is biliary-fecal, where 96.6% of administered drug is excreted in feces and 0% of the drug is excreted in the urine Label.
- Half-life
The elimination half life (t1/2) is approximately 13 hours Label.
- Clearance
Not Available
- Adverse Effects
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Pibrentasvir is not shown to be genotoxic according to in vitro or in vivo studies. It also shows to have no effect on mating, female or male fertility, or early embryonic development in rodent studies. Carcinogenicity studies with pibrentasvir have not been conducted Label.
- 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.
Drug Interaction Integrate drug-drug
interactions in your softwareAbacavir The metabolism of Abacavir can be decreased when combined with Pibrentasvir. Abemaciclib The serum concentration of Abemaciclib can be increased when it is combined with Pibrentasvir. Abrocitinib The serum concentration of Pibrentasvir can be increased when it is combined with Abrocitinib. Acetaminophen The metabolism of Acetaminophen can be decreased when combined with Pibrentasvir. Adagrasib The serum concentration of Pibrentasvir can be increased when it is combined with Adagrasib. - Food Interactions
- Avoid St. John's Wort. Co-administration may lead to decreased serum concentrations of pibrentasvir.
- Take with food.
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.- Mixture Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image Maviret Pibrentasvir (40 mg) + Glecaprevir (100 mg) Tablet, film coated Oral Abb Vie Deutschland Gmb H Co. Kg 2020-12-16 Not applicable EU 
Maviret Pibrentasvir (20 mg / sachet) + Glecaprevir (50 mg / sachet) Granule Oral Abbvie 2022-04-22 Not applicable Canada 
MAVIRET Pibrentasvir (40 MG) + Glecaprevir (100 MG) Tablet, film coated Oral Abbvie Deutschland Gmbh & Co. Kg 2017-10-05 Not applicable Italy 
Maviret Pibrentasvir (40 mg) + Glecaprevir (100 mg) Tablet Oral Abbvie 2017-09-13 Not applicable Canada MAVIRET (GLECAPREVIR 100MG/ PIBRENTASVIR 40MG) FILM COATED TABLETS Pibrentasvir (40 mg) + Glecaprevir (100 mg) Tablet, film coated Oral ABBVIE SDN BHD 2020-09-08 Not applicable Malaysia 
Categories
- ATC Codes
- J05AP57 — Glecaprevir and pibrentasvir
- Drug Categories
- Antiinfectives for Systemic Use
- Antiviral Agents
- Antivirals for Systemic Use
- Antivirals for treatment of HCV infections
- BCRP/ABCG2 Inhibitors
- BCRP/ABCG2 Substrates
- Cytochrome P-450 CYP1A2 Inhibitors
- Cytochrome P-450 CYP3A Inhibitors
- Cytochrome P-450 Enzyme Inhibitors
- Direct Acting Antivirals
- Hepatitis C Virus NS5A Inhibitor
- Heterocyclic Compounds, Fused-Ring
- OATP1B1/SLCO1B1 Inhibitors
- OATP1B3 inhibitors
- Organic Anion Transporting Polypeptide 1B1 Inhibitors
- Organic Anion Transporting Polypeptide 1B3 Inhibitors
- P-glycoprotein inhibitors
- P-glycoprotein substrates
- Treatments for Hepatitis C
- UGT1A1 Inhibitors
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as phenylpiperidines. These are compounds containing a phenylpiperidine skeleton, which consists of a piperidine bound to a phenyl group.
- Kingdom
- Organic compounds
- Super Class
- Organoheterocyclic compounds
- Class
- Piperidines
- Sub Class
- Phenylpiperidines
- Direct Parent
- Phenylpiperidines
- Alternative Parents
- Alpha amino acid amides / Phenylpyrrolidines / Benzimidazoles / Aniline and substituted anilines / N-acylpyrrolidines / Dialkylarylamines / Aralkylamines / Fluorobenzenes / Aryl fluorides / Tertiary carboxylic acid amides show 10 more
- Substituents
- 1-phenylpyrrolidine / 2-phenylpyrrolidine / Alpha-amino acid amide / Alpha-amino acid or derivatives / Amine / Amino acid or derivatives / Aniline or substituted anilines / Aralkylamine / Aromatic heteropolycyclic compound / Aryl fluoride show 32 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Hepatitis C Virus
Chemical Identifiers
- UNII
- 2WU922TK3L
- CAS number
- 1353900-92-1
- InChI Key
- VJYSBPDEJWLKKJ-NLIMODCCSA-N
- InChI
- InChI=1S/C57H65F5N10O8/c1-29(77-3)49(67-56(75)79-5)54(73)70-19-7-9-47(70)52-63-41-25-35(37(59)27-43(41)65-52)45-15-16-46(72(45)34-23-39(61)51(40(62)24-34)69-21-17-32(18-22-69)31-11-13-33(58)14-12-31)36-26-42-44(28-38(36)60)66-53(64-42)48-10-8-20-71(48)55(74)50(30(2)78-4)68-57(76)80-6/h11-14,23-30,32,45-50H,7-10,15-22H2,1-6H3,(H,63,65)(H,64,66)(H,67,75)(H,68,76)/t29-,30-,45-,46-,47+,48+,49+,50+/m1/s1
- IUPAC Name
- methyl N-[(2S,3R)-1-[(2S)-2-{5-[(2R,5R)-1-{3,5-difluoro-4-[4-(4-fluorophenyl)piperidin-1-yl]phenyl}-5-{6-fluoro-2-[(2S)-1-[(2S,3R)-3-methoxy-2-[(methoxycarbonyl)amino]butanoyl]pyrrolidin-2-yl]-1H-1,3-benzodiazol-5-yl}pyrrolidin-2-yl]-6-fluoro-1H-1,3-benzodiazol-2-yl}pyrrolidin-1-yl]-3-methoxy-1-oxobutan-2-yl]carbamate
- SMILES
- CO[C@H](C)[C@H](NC(=O)OC)C(=O)N1CCC[C@H]1C1=NC2=C(N1)C=C(F)C(=C2)[C@H]1CC[C@@H](N1C1=CC(F)=C(N2CCC(CC2)C2=CC=C(F)C=C2)C(F)=C1)C1=CC2=C(NC(=N2)[C@@H]2CCCN2C(=O)[C@@H](NC(=O)OC)[C@@H](C)OC)C=C1F
References
- General References
- Ng TI, Krishnan P, Pilot-Matias T, Kati W, Schnell G, Beyer J, Reisch T, Lu L, Dekhtyar T, Irvin M, Tripathi R, Maring C, Randolph JT, Wagner R, Collins C: In Vitro Antiviral Activity and Resistance Profile of the Next-Generation Hepatitis C Virus NS5A Inhibitor Pibrentasvir. Antimicrob Agents Chemother. 2017 Apr 24;61(5). pii: e02558-16. doi: 10.1128/AAC.02558-16. Print 2017 May. [Article]
- Masaki T, Suzuki R, Murakami K, Aizaki H, Ishii K, Murayama A, Date T, Matsuura Y, Miyamura T, Wakita T, Suzuki T: Interaction of hepatitis C virus nonstructural protein 5A with core protein is critical for the production of infectious virus particles. J Virol. 2008 Aug;82(16):7964-76. doi: 10.1128/JVI.00826-08. Epub 2008 Jun 4. [Article]
- FDA Press Announcements: FDA approves Mavyret for Hepatitis C [Link]
- FDA Approved Drug Products: MAVYRET (glecaprevir and pibrentasvir) tablets or pellets, for oral use [Link]
- Health Canada Approved Drug Products: MAVYRET (glecaprevir and pibrentasvir) tablets and granules, for oral use [Link]
- External Links
- PubChem Compound
- 58031952
- PubChem Substance
- 347829329
- ChemSpider
- 35013016
- 1940636
- ChEMBL
- CHEMBL3545123
- Wikipedia
- Pibrentasvir
- FDA label
- Download (925 KB)
Clinical Trials
- Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
Phase Status Purpose Conditions Count 4 Active Not Recruiting Treatment Heart Transplant Infection / Hepatitis C Virus (HCV) Infection / Transplanted Kidney Complication 1 4 Completed Basic Science Cardiovascular Disease (CVD) / Hepatitis C Virus (HCV) Infection / Human Immunodeficiency Virus (HIV) Infections 1 4 Completed Prevention Hepatitis C Virus (HCV) Infection / Renal Failure, Chronic Renal Failure 1 4 Completed Treatment Chronic Hepatitis C Virus (HCV) Infection / Chronic Kidney Disease (CKD) 1 4 Completed Treatment Chronic Kidney Disease (CKD) / Hepatitis C Virus (HCV) Infection / Kidney Failure 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Granule Oral Tablet Oral Tablet, coated Oral Tablet, film coated Oral 100.0 mg Pellet Oral Tablet, film coated Oral - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US9586978 Yes 2017-03-07 2030-12-10 US 
US8648037 Yes 2014-02-11 2032-07-19 US US9321807 Yes 2016-04-26 2035-12-05 US US8937150 Yes 2015-01-20 2032-11-18 US US10039754 Yes 2018-08-07 2030-12-10 US US10028937 Yes 2018-07-24 2030-12-10 US US10286029 Yes 2019-05-14 2034-09-14 US USRE48923 Yes 2015-11-08 2035-11-08 US US11246866 Yes 2016-12-24 2036-12-24 US US11484534 Yes 2014-09-14 2034-09-14 US
Properties
- State
- Solid
- Experimental Properties
Property Value Source water solubility <0.1 mg/mL FDA Label - Predicted Properties
Property Value Source Water Solubility 0.00557 mg/mL ALOGPS logP 5.95 ALOGPS logP 7.63 Chemaxon logS -5.3 ALOGPS pKa (Strongest Acidic) 10.66 Chemaxon pKa (Strongest Basic) 5.3 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 10 Chemaxon Hydrogen Donor Count 4 Chemaxon Polar Surface Area 199.58 Å2 Chemaxon Rotatable Bond Count 17 Chemaxon Refractivity 284.83 m3·mol-1 Chemaxon Polarizability 113.13 Å3 Chemaxon Number of Rings 10 Chemaxon Bioavailability 0 Chemaxon Rule of Five No Chemaxon Ghose Filter No Chemaxon Veber's Rule No Chemaxon MDDR-like Rule Yes Chemaxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 312.96408 predictedDeepCCS 1.0 (2019) [M+H]+ 314.68777 predictedDeepCCS 1.0 (2019) [M+Na]+ 320.89972 predictedDeepCCS 1.0 (2019)
Targets
- Kind
- Protein
- Organism
- Hepatitis C Virus
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Zinc ion binding
- Specific Function
- Not Available
- Gene Name
- NS5A
- Uniprot ID
- Q5L478
- Uniprot Name
- Nonstructural protein 5A
- Molecular Weight
- 48598.34 Da
Enzymes
- Kind
- Protein group
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- 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...
Components:
| Name | UniProt ID |
|---|---|
| Cytochrome P450 3A4 | P08684 |
| Cytochrome P450 3A43 | Q9HB55 |
| Cytochrome P450 3A5 | P20815 |
| Cytochrome P450 3A7 | P24462 |
References
- FDA Approved Drug Products: Mavyrettm (glecaprevir and pibrentasvir) tablets [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Steroid binding
- Specific Function
- UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform glucuronidates bilirubin IX-alpha to form both the...
- Gene Name
- UGT1A1
- Uniprot ID
- P22309
- Uniprot Name
- UDP-glucuronosyltransferase 1-1
- Molecular Weight
- 59590.91 Da
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- SubstrateInhibitor
- 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
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- SubstrateInhibitor
- General Function
- Xenobiotic-transporting atpase activity
- Specific Function
- High-capacity urate exporter functioning in both renal and extrarenal urate excretion. Plays a role in porphyrin homeostasis as it is able to mediates the export of protoporhyrin IX (PPIX) both fro...
- Gene Name
- ABCG2
- Uniprot ID
- Q9UNQ0
- Uniprot Name
- ATP-binding cassette sub-family G member 2
- Molecular Weight
- 72313.47 Da
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Sodium-independent organic anion transmembrane transporter activity
- Specific Function
- Mediates the Na(+)-independent uptake of organic anions such as pravastatin, taurocholate, methotrexate, dehydroepiandrosterone sulfate, 17-beta-glucuronosyl estradiol, estrone sulfate, prostagland...
- Gene Name
- SLCO1B1
- Uniprot ID
- Q9Y6L6
- Uniprot Name
- Solute carrier organic anion transporter family member 1B1
- Molecular Weight
- 76447.99 Da
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Sodium-independent organic anion transmembrane transporter activity
- Specific Function
- Mediates the Na(+)-independent uptake of organic anions such as 17-beta-glucuronosyl estradiol, taurocholate, triiodothyronine (T3), leukotriene C4, dehydroepiandrosterone sulfate (DHEAS), methotre...
- Gene Name
- SLCO1B3
- Uniprot ID
- Q9NPD5
- Uniprot Name
- Solute carrier organic anion transporter family member 1B3
- Molecular Weight
- 77402.175 Da
Drug created at August 31, 2017 15:29 / Updated at July 02, 2022 12:49