Identification

Name
Dasabuvir
Accession Number
DB09183
Type
Small Molecule
Groups
Approved
Description

Dasabuvir is a direct acting antiviral medication used as part of combination therapy to treat chronic Hepatitis C, an infectious liver disease caused by infection with Hepatitis C Virus (HCV). HCV is a single-stranded RNA virus that is categorized into nine distinct genotypes, with genotype 1 being the most common in the United States, and affecting 72% of all chronic HCV patients [8]. Treatment options for chronic Hepatitis C have advanced significantly since 2011, with the development of Direct Acting Antivirals (DAAs) such as Dasabuvir. Dasabuvir is a non-nucleoside NS5B inhibitor which binds to the palm domain of NS5B and induces a conformational change which renders the polymerase unable to elongate viral RNA [FDA Label]. The binding sites for non-nucleoside NS5B inhibitors are poorly conserved across HCV genotypes leading to the restriction of Dasabuvir's use to genotype 1 only.

In a joint recommendation published in 2016, the American Association for the Study of Liver Diseases (AASLD) and the Infectious Diseases Society of America (IDSA) recommend Dasabuvir as first line therapy in combination with Ombitasvir, Paritaprevir, and Ritonavir for genotype 1b and with Ribavirin for genotype 1a of Hepatitis C [8]. Dasabuvir, Ombitasvir, Paritaprevir, Ritonavir, and Ribavirin are used with the intent to cure, or achieve a sustained virologic response (SVR), after 12 weeks of therapy. SVR and eradication of HCV infection is associated with significant long-term health benefits including reduced liver-related damage, improved quality of life, reduced incidence of Hepatocellular Carcinoma, and reduced all-cause mortality [7].

Dasabuvir is available as a fixed dose combination product with Ombitasvir, Paritaprevir, and Ritonavir (tradename Viekira Pak) used for the treatment of chronic Hepatitis C. Approved in December 2014 by the FDA, Viekira Pak is indicated for the treatment of HCV genotype 1a with Ribavirin or genotype 1b without Ribavirin [FDA Label]. When combined together, Dasabuvir Ombitasvir, Paritaprevir, and Ritonavir as the combination product Viekira Pak have been shown to achieve a SVR of 100% for genotype 1b and 89% or 95% for genotype 1a after 12 weeks or 24 weeks of treatment including Ribavirin.

Structure
Thumb
Synonyms
  • Sodium 3-(3-tert-butyl-4-methoxy-5-{6­ [(methylsulfonyl)amino]naphthalene-2-yl}phenyl)-2,6-dioxo-3,6-dihydro-2H-pyrimidin-1-ide hydrate (1:1:1)
  • N-{6-[3-tert-butyl-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2-methoxyphenyl]naphthalen-2-yl}methanesulfonamide
External IDs
ABT 333 / ABT-333 / ABT333
Product Ingredients
IngredientUNIICASInChI Key
Dasabuvir sodiumR2M8F5TK9T1132940-11-4XHGMJAKIIJSQMF-UHFFFAOYSA-M
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
ExvieraTablet, film coated250 mgOralAbbvie2015-01-15Not applicableEu
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
Holkira PakDasabuvir (250 mg) + Ombitasvir (12.5 mg) + Paritaprevir (75 mg) + Ritonavir (50 mg)Kit; TabletOralAbbvie2015-01-06Not applicableCanada
Viekira PakDasabuvir + Ombitasvir + Paritaprevir + RitonavirKitAbbvie2014-12-19Not applicableUs
Viekira XRDasabuvir + Ombitasvir + Paritaprevir + RitonavirKitAbbvie2016-07-22Not applicableUs
Categories
UNII
DE54EQW8T1
CAS number
1132935-63-7
Weight
Average: 493.58
Monoisotopic: 493.167142155
Chemical Formula
C26H27N3O5S
InChI Key
NBRBXGKOEOGLOI-UHFFFAOYSA-N
InChI
InChI=1S/C26H27N3O5S/c1-26(2,3)22-15-20(29-11-10-23(30)27-25(29)31)14-21(24(22)34-4)18-7-6-17-13-19(28-35(5,32)33)9-8-16(17)12-18/h6-15,28H,1-5H3,(H,27,30,31)
IUPAC Name
N-{6-[3-tert-butyl-5-(2,4-dioxo-1,2,3,4-tetrahydropyrimidin-1-yl)-2-methoxyphenyl]naphthalen-2-yl}methanesulfonamide
SMILES
COC1=C(C=C(C=C1C1=CC2=CC=C(NS(C)(=O)=O)C=C2C=C1)N1C=CC(=O)NC1=O)C(C)(C)C

Pharmacology

Indication

Dasabuvir, in combination with Ombitasvir, Paritaprevir, and Ritonavir (as Viekira Pak) is indicated for the treatment of patients with HCV genotype 1a with Ribavirin or genotype 1b without Ribavirin including those with compensated cirrhosis [FDA Label].

Structured Indications
Pharmacodynamics

Dasabuvir is classified as a direct-acting antiviral (DAA) and prevents viral replication in HCV genotype 1 [FDA Label].

Mechanism of action

Dasabuvir is a non-nucleoside inhibitor of the HCV RNA-dependent RNA polymerase encoded by the NS5B gene, which is essential for replication of the viral genome [FDA Label]. Based on drug resistance mapping studies of HCV genotypes 1a and 1b, dasabuvir targets the palm domain of the NS5B polymerase, and is therefore referred to as a non-nucleoside NS5B-palm polymerase inhibitor. The EC50 values of dasabuvir against genotype 1a-H77 and 1b-Con1 strains in HCV replicon cell culture assays were 7.7 nM and 1.8 nM, respectively.

By binding to NS5b outside of the active site of the enzyme, dasabuvir induces a conformational change thereby preventing further elongation of the nascent viral genome [6]. A limitation of binding outside of the active site is that these binding sites are poorly preserved across the viral genotypes. This results in a limited potential for cross-genotypic activity and increased potential for development of resistance. Dasabuvir is therefore limited to treating genotypes 1a and 1b, and must be used in combination with other antiviral products.

TargetActionsOrganism
ANonstructural protein 5B (NS5B)
inhibitor
Absorption

Dasabuvir reaches peak plasma concentration 4 hours after administration [FDA Label]. The absolute bioavailability of Dasabuvir is 70%.

Volume of distribution

Dasabuvir has a volume of distribution at steady state of 149 liters [FDA Label].

Protein binding

Dasabuvir is greater than 99.5% bound to human plasma proteins [FDA Label].

Metabolism

Dasabuvir is predominantly metabolized by CYP2C8, and to a lesser extent by CYP3A [FDA Label].

Route of elimination

Dasabuvir is mainly excreted in the feces (94.4%) with very little excreted in the urine (2%) [FDA Label]. 26.2% and 0.03% of the drug excreted in the feces and urine respectively was present as the parent compound suggesting metabolism as the major elimination pathway.

Half life

The half-life of elimination of dasabuvir is 5.5 to 6 hours [FDA Label].

Clearance

Clearance of Dasabuvir has not been determined.

Toxicity

The most common adverse effects of Viekira Pak either in combination with or without Ribavirin were pruritus, nausea, insomnia, and asthenia [FDA Label].

Affected organisms
  • Hepatitis C Virus
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
AbirateroneThe serum concentration of Dasabuvir can be increased when it is combined with Abiraterone.Approved
AlfentanilThe serum concentration of Alfentanil can be increased when it is combined with Dasabuvir.Approved, Illicit
AlprazolamThe serum concentration of Alprazolam can be increased when it is combined with Dasabuvir.Approved, Illicit, Investigational
AmiodaroneThe serum concentration of Amiodarone can be increased when it is combined with Dasabuvir.Approved, Investigational
AprepitantThe serum concentration of Dasabuvir can be increased when it is combined with Aprepitant.Approved, Investigational
ArtemetherThe metabolism of Dasabuvir can be decreased when combined with Artemether.Approved
AtazanavirThe serum concentration of Dasabuvir can be increased when it is combined with Atazanavir.Approved, Investigational
AtomoxetineThe metabolism of Dasabuvir can be decreased when combined with Atomoxetine.Approved
AtorvastatinThe serum concentration of Atorvastatin can be increased when it is combined with Dasabuvir.Approved
BetaxololThe metabolism of Dasabuvir can be decreased when combined with Betaxolol.Approved
BoceprevirThe metabolism of Dasabuvir can be decreased when combined with Boceprevir.Approved, Withdrawn
BortezomibThe metabolism of Dasabuvir can be decreased when combined with Bortezomib.Approved, Investigational
BosentanThe serum concentration of Dasabuvir can be decreased when it is combined with Bosentan.Approved, Investigational
BuprenorphineThe serum concentration of Buprenorphine can be increased when it is combined with Dasabuvir.Approved, Illicit, Investigational, Vet Approved
BupropionThe metabolism of Dasabuvir can be decreased when combined with Bupropion.Approved
CarbamazepineThe metabolism of Dasabuvir can be increased when combined with Carbamazepine.Approved, Investigational
CelecoxibThe metabolism of Dasabuvir can be decreased when combined with Celecoxib.Approved, Investigational
CeritinibThe serum concentration of Dasabuvir can be increased when it is combined with Ceritinib.Approved
ChloroquineThe metabolism of Dasabuvir can be decreased when combined with Chloroquine.Approved, Vet Approved
ChlorpromazineThe metabolism of Dasabuvir can be decreased when combined with Chlorpromazine.Approved, Vet Approved
CholecalciferolThe metabolism of Dasabuvir can be decreased when combined with Cholecalciferol.Approved, Nutraceutical
CimetidineThe metabolism of Dasabuvir can be decreased when combined with Cimetidine.Approved
CinacalcetThe metabolism of Dasabuvir can be decreased when combined with Cinacalcet.Approved
CitalopramThe metabolism of Dasabuvir can be decreased when combined with Citalopram.Approved
ClarithromycinThe metabolism of Dasabuvir can be decreased when combined with Clarithromycin.Approved
ClemastineThe metabolism of Dasabuvir can be decreased when combined with Clemastine.Approved
ClobazamThe metabolism of Dasabuvir can be decreased when combined with Clobazam.Approved, Illicit
ClomipramineThe metabolism of Dasabuvir can be decreased when combined with Clomipramine.Approved, Vet Approved
ClotrimazoleThe metabolism of Dasabuvir can be decreased when combined with Clotrimazole.Approved, Vet Approved
ClozapineThe metabolism of Dasabuvir can be decreased when combined with Clozapine.Approved
CobicistatThe serum concentration of Dasabuvir can be increased when it is combined with Cobicistat.Approved
CocaineThe metabolism of Dasabuvir can be decreased when combined with Cocaine.Approved, Illicit
ConivaptanThe serum concentration of Dasabuvir can be increased when it is combined with Conivaptan.Approved, Investigational
CrisaboroleThe metabolism of Dasabuvir can be decreased when combined with Crisaborole.Approved
CrizotinibThe metabolism of Dasabuvir can be decreased when combined with Crizotinib.Approved
CyclosporineThe serum concentration of Cyclosporine can be increased when it is combined with Dasabuvir.Approved, Investigational, Vet Approved
DabrafenibThe serum concentration of Dasabuvir can be decreased when it is combined with Dabrafenib.Approved
DarifenacinThe metabolism of Dasabuvir can be decreased when combined with Darifenacin.Approved, Investigational
DarunavirThe serum concentration of Dasabuvir can be increased when it is combined with Darunavir.Approved
DasatinibThe serum concentration of Dasabuvir can be increased when it is combined with Dasatinib.Approved, Investigational
DeferasiroxThe serum concentration of Dasabuvir can be decreased when it is combined with Deferasirox.Approved, Investigational
DelavirdineThe metabolism of Dasabuvir can be decreased when combined with Delavirdine.Approved
DesipramineThe metabolism of Dasabuvir can be decreased when combined with Desipramine.Approved
DihydroergotamineThe metabolism of Dasabuvir can be decreased when combined with Dihydroergotamine.Approved
DiltiazemThe metabolism of Dasabuvir can be decreased when combined with Diltiazem.Approved
DiphenhydramineThe metabolism of Dasabuvir can be decreased when combined with Diphenhydramine.Approved
DosulepinThe metabolism of Dasabuvir can be decreased when combined with Dosulepin.Approved
DoxycyclineThe metabolism of Dasabuvir can be decreased when combined with Doxycycline.Approved, Investigational, Vet Approved
DronedaroneThe metabolism of Dasabuvir can be decreased when combined with Dronedarone.Approved
DuloxetineThe metabolism of Dasabuvir can be decreased when combined with Duloxetine.Approved
EfavirenzThe metabolism of Dasabuvir can be decreased when combined with Efavirenz.Approved, Investigational
EliglustatThe metabolism of Dasabuvir can be decreased when combined with Eliglustat.Approved
EnzalutamideThe serum concentration of Dasabuvir can be decreased when it is combined with Enzalutamide.Approved
ErythromycinThe metabolism of Dasabuvir can be decreased when combined with Erythromycin.Approved, Vet Approved
FelodipineThe metabolism of Dasabuvir can be decreased when combined with Felodipine.Approved, Investigational
FentanylThe serum concentration of Fentanyl can be increased when it is combined with Dasabuvir.Approved, Illicit, Investigational, Vet Approved
FluconazoleThe metabolism of Dasabuvir can be decreased when combined with Fluconazole.Approved
FluoxetineThe metabolism of Dasabuvir can be decreased when combined with Fluoxetine.Approved, Vet Approved
FluvastatinThe serum concentration of Fluvastatin can be increased when it is combined with Dasabuvir.Approved
FluvoxamineThe metabolism of Dasabuvir can be decreased when combined with Fluvoxamine.Approved, Investigational
FosamprenavirThe metabolism of Dasabuvir can be decreased when combined with Fosamprenavir.Approved
FosaprepitantThe serum concentration of Dasabuvir can be increased when it is combined with Fosaprepitant.Approved
FosphenytoinThe metabolism of Dasabuvir can be increased when combined with Fosphenytoin.Approved
Fusidic AcidThe serum concentration of Dasabuvir can be increased when it is combined with Fusidic Acid.Approved
HaloperidolThe metabolism of Dasabuvir can be decreased when combined with Haloperidol.Approved
ImatinibThe metabolism of Dasabuvir can be decreased when combined with Imatinib.Approved
ImipramineThe metabolism of Dasabuvir can be decreased when combined with Imipramine.Approved
IndinavirThe metabolism of Dasabuvir can be decreased when combined with Indinavir.Approved
IrbesartanThe metabolism of Dasabuvir can be decreased when combined with Irbesartan.Approved, Investigational
IsavuconazoniumThe metabolism of Dasabuvir can be decreased when combined with Isavuconazonium.Approved, Investigational
IsoniazidThe metabolism of Dasabuvir can be decreased when combined with Isoniazid.Approved
IsradipineThe metabolism of Dasabuvir can be decreased when combined with Isradipine.Approved
ItraconazoleThe metabolism of Dasabuvir can be decreased when combined with Itraconazole.Approved, Investigational
IvacaftorThe serum concentration of Dasabuvir can be increased when it is combined with Ivacaftor.Approved
KetoconazoleThe metabolism of Dasabuvir can be decreased when combined with Ketoconazole.Approved, Investigational
LapatinibThe metabolism of Dasabuvir can be decreased when combined with Lapatinib.Approved, Investigational
LopinavirThe metabolism of Dasabuvir can be decreased when combined with Lopinavir.Approved
LorcaserinThe metabolism of Dasabuvir can be decreased when combined with Lorcaserin.Approved
LosartanThe metabolism of Dasabuvir can be decreased when combined with Losartan.Approved
LovastatinThe metabolism of Dasabuvir can be decreased when combined with Lovastatin.Approved, Investigational
LuliconazoleThe serum concentration of Dasabuvir can be increased when it is combined with Luliconazole.Approved
LumacaftorThe serum concentration of Dasabuvir can be increased when it is combined with Lumacaftor.Approved
LumefantrineThe metabolism of Dasabuvir can be decreased when combined with Lumefantrine.Approved
ManidipineThe metabolism of Dasabuvir can be decreased when combined with Manidipine.Approved, Investigational
MethadoneThe metabolism of Dasabuvir can be decreased when combined with Methadone.Approved
MethotrimeprazineThe metabolism of Dasabuvir can be decreased when combined with Methotrimeprazine.Approved
MetoprololThe metabolism of Dasabuvir can be decreased when combined with Metoprolol.Approved, Investigational
MidostaurinThe metabolism of Dasabuvir can be decreased when combined with Midostaurin.Approved
MifepristoneThe serum concentration of Dasabuvir can be increased when it is combined with Mifepristone.Approved, Investigational
MirabegronThe metabolism of Dasabuvir can be decreased when combined with Mirabegron.Approved
MitotaneThe serum concentration of Dasabuvir can be decreased when it is combined with Mitotane.Approved
NefazodoneThe metabolism of Dasabuvir can be decreased when combined with Nefazodone.Approved, Withdrawn
NelfinavirThe metabolism of Dasabuvir can be decreased when combined with Nelfinavir.Approved
NetupitantThe serum concentration of Dasabuvir can be increased when it is combined with Netupitant.Approved
NevirapineThe metabolism of Dasabuvir can be increased when combined with Nevirapine.Approved
NicardipineThe metabolism of Dasabuvir can be decreased when combined with Nicardipine.Approved
NilotinibThe metabolism of Dasabuvir can be decreased when combined with Nilotinib.Approved, Investigational
OlaparibThe metabolism of Dasabuvir can be decreased when combined with Olaparib.Approved
OsimertinibThe serum concentration of Dasabuvir can be increased when it is combined with Osimertinib.Approved
PalbociclibThe serum concentration of Dasabuvir can be increased when it is combined with Palbociclib.Approved
PanobinostatThe serum concentration of Dasabuvir can be increased when it is combined with Panobinostat.Approved, Investigational
ParoxetineThe metabolism of Dasabuvir can be decreased when combined with Paroxetine.Approved, Investigational
PazopanibThe serum concentration of Pazopanib can be increased when it is combined with Dasabuvir.Approved
Peginterferon alfa-2bThe serum concentration of Dasabuvir can be decreased when it is combined with Peginterferon alfa-2b.Approved
PentobarbitalThe metabolism of Dasabuvir can be increased when combined with Pentobarbital.Approved, Vet Approved
PhenobarbitalThe metabolism of Dasabuvir can be increased when combined with Phenobarbital.Approved
PhenytoinThe metabolism of Dasabuvir can be increased when combined with Phenytoin.Approved, Vet Approved
PioglitazoneThe metabolism of Dasabuvir can be decreased when combined with Pioglitazone.Approved, Investigational
PitavastatinThe serum concentration of Pitavastatin can be increased when it is combined with Dasabuvir.Approved
PosaconazoleThe metabolism of Dasabuvir can be decreased when combined with Posaconazole.Approved, Investigational, Vet Approved
PrimidoneThe metabolism of Dasabuvir can be increased when combined with Primidone.Approved, Vet Approved
PromazineThe metabolism of Dasabuvir can be decreased when combined with Promazine.Approved, Vet Approved
QuinidineThe serum concentration of Quinidine can be increased when it is combined with Dasabuvir.Approved
QuinineThe metabolism of Dasabuvir can be decreased when combined with Quinine.Approved
RabeprazoleThe metabolism of Dasabuvir can be decreased when combined with Rabeprazole.Approved, Investigational
RanolazineThe metabolism of Dasabuvir can be decreased when combined with Ranolazine.Approved, Investigational
RifabutinThe metabolism of Dasabuvir can be increased when combined with Rifabutin.Approved
RifampicinThe metabolism of Dasabuvir can be increased when combined with Rifampicin.Approved
RifapentineThe metabolism of Dasabuvir can be increased when combined with Rifapentine.Approved
RitonavirThe metabolism of Dasabuvir can be decreased when combined with Ritonavir.Approved, Investigational
RolapitantThe metabolism of Dasabuvir can be decreased when combined with Rolapitant.Approved
RopiniroleThe metabolism of Dasabuvir can be decreased when combined with Ropinirole.Approved, Investigational
RosiglitazoneThe metabolism of Dasabuvir can be decreased when combined with Rosiglitazone.Approved, Investigational
RosuvastatinThe serum concentration of Rosuvastatin can be increased when it is combined with Dasabuvir.Approved
SaquinavirThe metabolism of Dasabuvir can be decreased when combined with Saquinavir.Approved, Investigational
SecobarbitalThe metabolism of Dasabuvir can be increased when combined with Secobarbital.Approved, Vet Approved
SertralineThe metabolism of Dasabuvir can be decreased when combined with Sertraline.Approved
SildenafilThe metabolism of Dasabuvir can be decreased when combined with Sildenafil.Approved, Investigational
SiltuximabThe serum concentration of Dasabuvir can be decreased when it is combined with Siltuximab.Approved
SimeprevirThe serum concentration of Dasabuvir can be increased when it is combined with Simeprevir.Approved
SirolimusThe serum concentration of Sirolimus can be increased when it is combined with Dasabuvir.Approved, Investigational
St. John's WortThe serum concentration of Dasabuvir can be decreased when it is combined with St. John's Wort.Investigational, Nutraceutical
StiripentolThe serum concentration of Dasabuvir can be increased when it is combined with Stiripentol.Approved
SulfamethoxazoleThe metabolism of Dasabuvir can be decreased when combined with Sulfamethoxazole.Approved
SulfisoxazoleThe metabolism of Dasabuvir can be decreased when combined with Sulfisoxazole.Approved, Vet Approved
TacrolimusThe serum concentration of Tacrolimus can be increased when it is combined with Dasabuvir.Approved, Investigational
TamoxifenThe metabolism of Dasabuvir can be decreased when combined with Tamoxifen.Approved
TelaprevirThe metabolism of Dasabuvir can be decreased when combined with Telaprevir.Approved, Withdrawn
TelithromycinThe metabolism of Dasabuvir can be decreased when combined with Telithromycin.Approved
TerbinafineThe metabolism of Dasabuvir can be decreased when combined with Terbinafine.Approved, Investigational, Vet Approved
TeriflunomideThe metabolism of Dasabuvir can be decreased when combined with Teriflunomide.Approved
ThioridazineThe metabolism of Dasabuvir can be decreased when combined with Thioridazine.Approved, Withdrawn
TiclopidineThe metabolism of Dasabuvir can be decreased when combined with Ticlopidine.Approved
TipranavirThe metabolism of Dasabuvir can be decreased when combined with Tipranavir.Approved, Investigational
TocilizumabThe serum concentration of Dasabuvir can be decreased when it is combined with Tocilizumab.Approved
TopiroxostatThe metabolism of Dasabuvir can be decreased when combined with Topiroxostat.Approved, Investigational
TopotecanThe serum concentration of Topotecan can be increased when it is combined with Dasabuvir.Approved, Investigational
TranylcypromineThe metabolism of Dasabuvir can be decreased when combined with Tranylcypromine.Approved
TrimethoprimThe metabolism of Dasabuvir can be decreased when combined with Trimethoprim.Approved, Vet Approved
VenlafaxineThe metabolism of Dasabuvir can be decreased when combined with Venlafaxine.Approved
VerapamilThe metabolism of Dasabuvir can be decreased when combined with Verapamil.Approved
VoriconazoleThe metabolism of Dasabuvir can be decreased when combined with Voriconazole.Approved, Investigational
ZiprasidoneThe metabolism of Dasabuvir can be decreased when combined with Ziprasidone.Approved
Food Interactions
Not Available

References

General References
  1. Gentile I, Buonomo AR, Borgia G: Dasabuvir: A Non-Nucleoside Inhibitor of NS5B for the Treatment of Hepatitis C Virus Infection. Rev Recent Clin Trials. 2014;9(2):115-23. [PubMed:24882169]
  2. Trivella JP, Gutierrez J, Martin P: Dasabuvir : a new direct antiviral agent for the treatment of hepatitis C. Expert Opin Pharmacother. 2015 Mar;16(4):617-24. doi: 10.1517/14656566.2015.1012493. Epub 2015 Feb 9. [PubMed:25665437]
  3. Mantry PS, Pathak L: Dasabuvir (ABT333) for the treatment of chronic HCV genotype I: a new face of cure, an expert review. Expert Rev Anti Infect Ther. 2016 Feb;14(2):157-65. doi: 10.1586/14787210.2016.1120668. Epub 2015 Dec 17. [PubMed:26567871]
  4. McConachie SM, Wilhelm SM, Kale-Pradhan PB: New direct-acting antivirals in hepatitis C therapy: a review of sofosbuvir, ledipasvir, daclatasvir, simeprevir, paritaprevir, ombitasvir and dasabuvir. Expert Rev Clin Pharmacol. 2016 Feb;9(2):287-302. doi: 10.1586/17512433.2016.1129272. Epub 2016 Jan 8. [PubMed:26651915]
  5. Shen J, Serby M, Reed A, Lee AJ, Menon R, Zhang X, Marsh K, Wan X, Kavetskaia O, Fischer V: Metabolism and Disposition of Hepatitis C Polymerase Inhibitor Dasabuvir in Humans. Drug Metab Dispos. 2016 Aug;44(8):1139-47. doi: 10.1124/dmd.115.067512. Epub 2016 May 13. [PubMed:27179126]
  6. Bagaglio S, Uberti-Foppa C, Morsica G: Resistance Mechanisms in Hepatitis C Virus: implications for Direct-Acting Antiviral Use. Drugs. 2017 May 12. doi: 10.1007/s40265-017-0753-x. [PubMed:28497432]
  7. Myers RP, Shah H, Burak KW, Cooper C, Feld JJ: An update on the management of chronic hepatitis C: 2015 Consensus guidelines from the Canadian Association for the Study of the Liver. Can J Gastroenterol Hepatol. 2015 Jan-Feb;29(1):19-34. Epub 2015 Jan 13. [PubMed:25585348]
  8. American Association for the Study of Liver Diseases; Infectious Diseases Society of America. HCV guidance. http://hcvguidelines.org. Accessed June 12, 2017. [Link]
External Links
KEGG Drug
D10582
PubChem Compound
56640146
PubChem Substance
310265091
ChemSpider
29776744
ChEBI
85182
ChEMBL
CHEMBL3137312
PharmGKB
PA166163411
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Dasabuvir
ATC Codes
J05AX66 — Dasabuvir, ombitasvir, paritaprevir and ritonavirJ05AX16 — Dasabuvir
FDA label
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Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedNot AvailableHCV Infections2
1CompletedNot AvailableRelative Bioavailability1
1CompletedOtherHCV Infections1
1CompletedTreatmentHCV Infections2
1CompletedTreatmentHealthy Volunteers1
2CompletedNot AvailableHCV Infections1
2CompletedTreatmentChronic Hepatitis C Infection3
2CompletedTreatmentChronic Hepatitis C Infection / Chronic Hepatitis C Virus (HCV) Infection1
2CompletedTreatmentChronic Hepatitis C Infection / HCV / Hepatitis C Genotype 11
2CompletedTreatmentChronic Hepatitis C Infection / Hepatitis C Virus (HCV)1
2CompletedTreatmentChronic Hepatitis C Virus (HCV) Infection / Hepatitis C (HCV) / Hepatitis C Genotype 11
2CompletedTreatmentChronic Hepatitis C Virus (HCV) Infection / Hepatitis C (HCV) / Hepatitis C Genotype 1a1
2CompletedTreatmentChronic Hepatitis C Virus (HCV) Infection / Compensated liver disease / Hepatitis C Virus (HCV)1
2CompletedTreatmentChronic Hepatitis C Virus Infection1
2RecruitingTreatmentHuman Immunodeficiency Virus (HIV) Infections1
2, 3CompletedTreatmentChronic Hepatitis C Virus (HCV) Infection / Compensated Cirrhosis and Non-cirrhotics / Hepatitis C Virus Infection / Human Immunodeficiency Virus (HIV) Infections1
2, 3RecruitingTreatmentChronic Hepatitis C Infection / HBV Coinfection / Hepatitis B Reactivation1
3Active Not RecruitingTreatmentChronic Hepatitis C Genotype 12
3CompletedOtherChronic Hepatitis C Infection1
3CompletedTreatmentChronic Hepatitis C Infection9
3CompletedTreatmentChronic Hepatitis C Infection / Chronic Hepatitis C Virus (HCV) Infection1
3CompletedTreatmentChronic Hepatitis C Infection / Chronic Kidney Disease (CKD) / Genotype 1a / Genotype 4 / HCV / Hepatitis C Virus (HCV) / IFN / PegIFN1
3CompletedTreatmentChronic Hepatitis C Infection / Hepatitis C Virus (HCV)1
3CompletedTreatmentChronic Hepatitis C Infection / Compensated liver disease / Hepatitis C Virus (HCV)1
3CompletedTreatmentChronic Hepatitis C Virus1
3CompletedTreatmentChronic Hepatitis C Virus (HCV Infection Genotype 1)1
3CompletedTreatmentChronic Hepatitis C Virus (HCV) Infection / Cirrhosis, Decompensated / Hepatitis C Virus (HCV)1
3CompletedTreatmentChronic Hepatitis C Virus (HCV) Infection / Compensated liver disease / End-Stage Renal Disease (ESRD) / Hepatitis C Virus (HCV) / Severe Renal Impairment1
3CompletedTreatmentChronic Hepatitis C Virus (HCV) Infection / Hepatitis C (HCV) / Hepatitis C Genotype 1a1
3CompletedTreatmentChronic Hepatitis C Virus (HCV) Infection / Hepatitis C Virus (HCV) / Liver Cirrhosis1
3CompletedTreatmentChronic Hepatitis C Virus / Hepatitis C Virus (HCV)1
3CompletedTreatmentHepatitis C Infection / Hepatitis C Virus (HCV)1
3RecruitingTreatmentChronic Hepatitis C Infection1
3RecruitingTreatmentHepatitis C, Acute1
4Active Not RecruitingTreatmentHepatitis C Virus (HCV)1
4Active Not RecruitingTreatmentHepatitis C, Chronic1
4Not Yet RecruitingTreatmentChronic Hepatitis, C Virus1
4RecruitingTreatmentChronic Hepatitis C Virus (HCV) Infection1
4RecruitingTreatmentHCV Coinfection1
4RecruitingTreatmentHepatitis C, Chronic1
4RecruitingTreatmentHepatitis Viruses1
Not AvailableActive Not RecruitingNot AvailableChronic Hepatitis C Virus (HCV) Infection / Liver Cirrhosis1
Not AvailableRecruitingNot AvailableChronic Hepatitis C Infection1
Not AvailableRecruitingNot AvailableHepatitis C Infection1
Not AvailableRecruitingNot AvailableHepatitis C, Chronic / Human Immunodeficiency Virus (HIV)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
Tablet, film coatedOral250 mg
Kit; tabletOral
Kit
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US6703403Yes1996-12-262016-12-26Us
US6037157Yes1996-12-262016-12-26Us
US7364752Yes2001-05-102021-05-10Us
US7148359Yes2000-01-192020-01-19Us
US8268349Yes2005-02-252025-02-25Us
US8399015Yes2005-02-252025-02-25Us
US9139536No2008-11-092028-11-09Us
US8685984No2012-09-042032-09-04Us
US8466159No2012-09-042032-09-04Us
US8642538No2009-09-102029-09-10Us
US8501238No2008-09-172028-09-17Us
US8680106No2012-09-042032-09-04Us
US8492386No2012-09-042032-09-04Us
US8188104No2009-05-172029-05-17Us
US9006387No2010-06-102030-06-10Us
US9044480No2011-04-102031-04-10Us
US8686026No2011-06-092031-06-09Us
US8420596Yes2011-10-102031-10-10Us
US8691938No2012-04-132032-04-13Us
US9629841No2013-10-182033-10-18Us
US9333204No2015-01-022035-01-02Us
US9744170No2015-01-022035-01-02Us

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.000799 mg/mLALOGPS
logP4.7ALOGPS
logP3.42ChemAxon
logS-5.8ALOGPS
pKa (Strongest Acidic)9.09ChemAxon
pKa (Strongest Basic)-4.8ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area104.81 Å2ChemAxon
Rotatable Bond Count5ChemAxon
Refractivity134.04 m3·mol-1ChemAxon
Polarizability53.19 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
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/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as phenylnaphthalenes. These are compounds containing a phenylnaphthalene skeleton, which consists of a naphthalene bound to a phenyl group.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Naphthalenes
Sub Class
Phenylnaphthalenes
Direct Parent
Phenylnaphthalenes
Alternative Parents
Sulfanilides / Methoxyanilines / Phenylpropanes / Phenoxy compounds / Anisoles / Methoxybenzenes / Pyrimidones / Alkyl aryl ethers / Organosulfonamides / Organic sulfonamides
show 11 more
Substituents
Phenylnaphthalene / Sulfanilide / Phenylpropane / Methoxyaniline / Phenoxy compound / Anisole / Phenol ether / Methoxybenzene / Alkyl aryl ether / Pyrimidone
show 25 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
aromatic ether, sulfonamide, pyrimidone, ring assembly, naphthalenes (CHEBI:85182)

Targets

Kind
Protein
Organism
Not Available
Pharmacological action
Yes
Actions
Inhibitor
General Function
Not Available
Specific Function
Rna binding
Gene Name
NS5b
Uniprot ID
P87764
Uniprot Name
Nonstructural protein 5b
Molecular Weight
Not Available
References
  1. Soriano V, Vispo E, de Mendoza C, Labarga P, Fernandez-Montero JV, Poveda E, Trevino A, Barreiro P: Hepatitis C therapy with HCV NS5B polymerase inhibitors. Expert Opin Pharmacother. 2013 Jun;14(9):1161-70. doi: 10.1517/14656566.2013.795543. Epub 2013 Apr 27. [PubMed:23621117]
  2. Mantry PS, Pathak L: Dasabuvir (ABT333) for the treatment of chronic HCV genotype I: a new face of cure, an expert review. Expert Rev Anti Infect Ther. 2016 Feb;14(2):157-65. doi: 10.1586/14787210.2016.1120668. Epub 2015 Dec 17. [PubMed:26567871]
  3. Trivella JP, Gutierrez J, Martin P: Dasabuvir : a new direct antiviral agent for the treatment of hepatitis C. Expert Opin Pharmacother. 2015 Mar;16(4):617-24. doi: 10.1517/14656566.2015.1012493. Epub 2015 Feb 9. [PubMed:25665437]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
No
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
CYP2C8
Uniprot ID
P10632
Uniprot Name
Cytochrome P450 2C8
Molecular Weight
55824.275 Da
References
  1. Shen J, Serby M, Reed A, Lee AJ, Menon R, Zhang X, Marsh K, Wan X, Kavetskaia O, Fischer V: Metabolism and Disposition of Hepatitis C Polymerase Inhibitor Dasabuvir in Humans. Drug Metab Dispos. 2016 Aug;44(8):1139-47. doi: 10.1124/dmd.115.067512. Epub 2016 May 13. [PubMed:27179126]
Kind
Protein
Organism
Human
Pharmacological action
No
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. Shen J, Serby M, Reed A, Lee AJ, Menon R, Zhang X, Marsh K, Wan X, Kavetskaia O, Fischer V: Metabolism and Disposition of Hepatitis C Polymerase Inhibitor Dasabuvir in Humans. Drug Metab Dispos. 2016 Aug;44(8):1139-47. doi: 10.1124/dmd.115.067512. Epub 2016 May 13. [PubMed:27179126]
Kind
Protein
Organism
Human
Pharmacological action
No
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. Shen J, Serby M, Reed A, Lee AJ, Menon R, Zhang X, Marsh K, Wan X, Kavetskaia O, Fischer V: Metabolism and Disposition of Hepatitis C Polymerase Inhibitor Dasabuvir in Humans. Drug Metab Dispos. 2016 Aug;44(8):1139-47. doi: 10.1124/dmd.115.067512. Epub 2016 May 13. [PubMed:27179126]
4. UDP-glucuronosyltransferase 1A1
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor

Transporters

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
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
Human
Pharmacological action
No
Actions
Substrate
General Function
Efflux transmembrane transporter activity
Specific Function
Drug efflux transporter present in a number of stem cells that acts as a regulator of cellular differentiation. Able to mediate efflux from cells of the rhodamine dye and of the therapeutic drug do...
Gene Name
ABCB5
Uniprot ID
Q2M3G0
Uniprot Name
ATP-binding cassette sub-family B member 5
Molecular Weight
138639.48 Da

Drug created on October 15, 2015 12:45 / Updated on December 01, 2017 17:24