Identification

Name
Paritaprevir
Accession Number
DB09297
Type
Small Molecule
Groups
Approved
Description

Paritaprevir 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 paritaprevir. As a newer generation and directly acting HCV antiviral, paritaprevir products have better Sustained Virological Response (SVR) rates, higher barriers to resistance, fewer side effects, and a reduced pill burden compared to older agents such as Boceprevir, Telaprevir, Peginterferon alfa-2a, Peginterferon alfa-2b, and Ribavirin. By combining multiple antiretroviral medications into fixed dose products, the viral lifecycle can be targeted at multiple stages while simultaneously reducing the risk of developing resistant viral strains [7]. Within Canada and the United States, paritaprevir is currently available in three fixed dose products: Viekira Pak (FDA), Technivie (FDA and Health Canada), and Holkira Pak (Health Canada).

More specifically, paritaprevir prevents viral replication by inhibiting the NS3/4A serine protease of Hepatitis C Virus (HCV) [FDA Label]. Following viral replication of HCV genetic material and translation into a single polypeptide, Nonstructural Protein 3 (NS3) and its activating cofactor Nonstructural Protein 4A (NS4A) are responsible for cleaving genetic material into the following structural and nonstructural proteins required for assembly into mature virus: NS3, NS4A, NS4B, NS5A, and NS5B [6]. By inhibiting viral protease NS3/4A, paritaprevir therefore prevents viral replication and function.

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 Paritaprevir as a first line therapy option when used in combination with other antivirals for genotypes 1a, 1b, and 4[8]. Depending on the genotype, Paritaprevir is often used in combination with other antivirals such as Ombitasvir, Dasabuvir, Ritonavir, and Ribavirin, with the intent to cure, or achieve a sustained virologic response (SVR), after 12 weeks of daily 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 [4]. Treatment with direct acting antivirals such as paritaprevir is associated with very minimal side effects, with the most common being headache and fatigue [FDA Label]. Lack of significant side effects and short duration of therapy is a considerable advantage over older interferon-based regimens, which were limited by infusion site reactions, reduced blood count, and neuropsychiatric effects [5].

Paritaprevir first came on the market as a fixed-dose combination product with Ombitasvir, Dasabuvir, and Ritonavir as the FDA-approved product Viekira Pak. First approved in December 2014, Viekira Pak is indicated for the treatment of HCV genotype 1b without cirrhosis or with compensated cirrhosis, and when combined with Ribavirin for the treatment of HCV genotype 1a without cirrhosis or with compensated cirrhosis.

Paritaprevir is also available as a fixed-dose combination product with Ombitasvir and Ritonavir as the FDA- and Health Canada-approved product Technivie. First approved in July 2015, Technivie is indicated in combination with Ribavirin for the treatment of patients with genotype 4 chronic hepatitis C virus (HCV) infection without cirrhosis or with compensated cirrhosis.

In Canada, paritaprevir is also available as a fixed-dose combination product with Ombitasvir, Dasabuvir, and Ritonavir as the Health Canada-approved, commercially available product Holkira Pak. First approved in January 2015, Holkira Pak is indicated for the treatment of HCV genotype 1b with or without cirrhosis, and when combined with Ribavirin for the treatment of HCV genotype 1a with or without cirrhosis.

Structure
Thumb
Synonyms
  • (2R,6S,12Z,13aR,14aR,16aS)-N-(cyclopropanesulfonyl)-6-[(5-methylpyrazine-2-carbonyl)amino]-5,16-dioxo-2-[(phenanthridin-6-yl)oxy]-1,2,3,6,7,8,9,10,11,13a,14,15,16,16a-tetradecahydrocyclopropa[e]pyrrolo[1,2-a][1,4]diazacyclopentadecine-14a(5H)-carboxamide
  • Veruprevir
External IDs
ABT 450 / ABT-450 / ABT450
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
Holkira PakParitaprevir (75 mg) + Dasabuvir (250 mg) + Ombitasvir (12.5 mg) + Ritonavir (50 mg)Kit; TabletOralAbbvie2015-01-06Not applicableCanada
TechnivieParitaprevir (75 mg) + Ombitasvir (12.5 mg) + Ritonavir (50 mg)TabletOralAbbvie2015-11-24Not applicableCanada
TechnivieParitaprevir + Ombitasvir + RitonavirKitAbbvie2015-07-24Not applicableUs
Viekira PakParitaprevir + Dasabuvir + Ombitasvir + RitonavirKitAbbvie2014-12-19Not applicableUs
Viekira XRParitaprevir + Dasabuvir + Ombitasvir + RitonavirKitAbbvie2016-07-22Not applicableUs
Categories
UNII
OU2YM37K86
CAS number
1216941-48-8
Weight
Average: 765.89
Monoisotopic: 765.294467927
Chemical Formula
C40H43N7O7S
InChI Key
UAUIUKWPKRJZJV-MDJGTQRPSA-N
InChI
InChI=1S/C40H43N7O7S/c1-24-21-42-33(22-41-24)35(48)43-32-16-6-4-2-3-5-11-25-20-40(25,39(51)46-55(52,53)27-17-18-27)45-36(49)34-19-26(23-47(34)38(32)50)54-37-30-14-8-7-12-28(30)29-13-9-10-15-31(29)44-37/h5,7-15,21-22,25-27,32,34H,2-4,6,16-20,23H2,1H3,(H,43,48)(H,45,49)(H,46,51)/b11-5-/t25-,26+,32-,34-,40+/m0/s1
IUPAC Name
(1S,4R,6R,7Z,14S,18R)-N-(cyclopropanesulfonyl)-14-(5-methylpyrazine-2-amido)-2,15-dioxo-18-(phenanthridin-6-yloxy)-3,16-diazatricyclo[14.3.0.0⁴,⁶]nonadec-7-ene-4-carboxamide
SMILES
[H][[email protected]]12C[[email protected]]1(NC(=O)[[email protected]]1([H])C[[email protected]](CN1C(=O)[[email protected]](CCCCC\C=C/2)NC(=O)C1=NC=C(C)N=C1)OC1=NC2=CC=CC=C2C2=CC=CC=C12)C(=O)NS(=O)(=O)C1CC1

Pharmacology

Indication

When used within the fixed-dose combination product with Ombitasvir, Dasabuvir, and Ritonavir as the FDA-approved product Viekira Pak, paritaprevir is indicated for the treatment of HCV genotype 1b without cirrhosis or with compensated cirrhosis, and when combined with Ribavirin for the treatment of HCV genotype 1a without cirrhosis or with compensated cirrhosis.

When used within the fixed-dose combination product with Ombitasvir and Ritonavir as the FDA- and Health Canada-approved product Technivie, paritaprevir is indicated in combination with Ribavirin for the treatment of patients with genotype 4 chronic hepatitis C virus (HCV) infection without cirrhosis or with compensated cirrhosis.

When used within the fixed-dose combination product with Ombitasvir, Dasabuvir, and Ritonavir as the Health Canada-approved, commercially available product Holkira Pak, paritaprevir is indicated for the treatment of HCV genotype 1b with or without cirrhosis, and when combined with Ribavirin for the treatment of HCV genotype 1a with or without cirrhosis.

Structured Indications
Pharmacodynamics

At concentrations approximately 6 and 1.8 times the therapeutic concentrations of paritaprevir and ombitasvir, the combination did not prolong QTc to any clinically relevant extent [FDA Label].

Mechanism of action

Paritaprevir is a potent inhibitor of the NS3/4A serine protease of Hepatitis C Virus (HCV) [FDA Label]. Following viral replication of HCV genetic material and translation into a single polypeptide, Nonstructural Protein 3 (NS3) and its activating cofactor Nonstructural Protein 4A (NS4A) are responsible for cleaving it into the following structural and nonstructural proteins required for assembly into mature virus: NS3, NS4A, NS4B, NS5A, and NS5B. By inhibiting viral protease NS3/4A, paritaprevir therefore prevents viral replication and function.

TargetActionsOrganism
ANS3/4A protein
inhibitor
Hepatitis C virus
Absorption

Tmax of approximately 4 to 5 hours with a maximum concentration (Cmax) of 194 ng/mL [FDA Label].

Volume of distribution

Volume of distribution at steady state is approximately 103 L [FDA Label].

Protein binding

97 to 98.6% bound to human plasma proteins [FDA Label].

Metabolism

Paritaprevir is predominantly metabolized by CYP3A4 and to a lesser extent by CYP3A5 [FDA Label].

Route of elimination

Following a single dose administration of 14C-paritaprevir co-dosed with 100 mg of ritonavir, approximately 88% of the radioactivity was recovered in feces with limited radioactivity (8.8%) in urine; unchanged paritaprevir accounted for 1.1% of the radioactivity in the feces and 0.05% in the urine [FDA Label].

Half life

5.5 hr [FDA Label]

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

Interactions

Drug Interactions
DrugInteractionDrug group
AlfentanilThe serum concentration of Alfentanil can be increased when it is combined with Paritaprevir.Approved, Illicit
AlprazolamThe serum concentration of Alprazolam can be increased when it is combined with Paritaprevir.Approved, Illicit, Investigational
AmiodaroneThe serum concentration of Amiodarone can be increased when it is combined with Paritaprevir.Approved, Investigational
AprepitantThe serum concentration of Paritaprevir can be increased when it is combined with Aprepitant.Approved, Investigational
AtomoxetineThe metabolism of Paritaprevir can be decreased when combined with Atomoxetine.Approved
AtorvastatinThe serum concentration of Atorvastatin can be increased when it is combined with Paritaprevir.Approved
BoceprevirThe metabolism of Paritaprevir can be decreased when combined with Boceprevir.Approved, Withdrawn
BortezomibThe metabolism of Paritaprevir can be decreased when combined with Bortezomib.Approved, Investigational
BosentanThe serum concentration of Paritaprevir can be decreased when it is combined with Bosentan.Approved, Investigational
BuprenorphineThe serum concentration of Buprenorphine can be increased when it is combined with Paritaprevir.Approved, Illicit, Investigational, Vet Approved
CarbamazepineThe metabolism of Paritaprevir can be increased when combined with Carbamazepine.Approved, Investigational
CeritinibThe serum concentration of Paritaprevir can be increased when it is combined with Ceritinib.Approved
ClarithromycinThe metabolism of Paritaprevir can be decreased when combined with Clarithromycin.Approved
ClemastineThe metabolism of Paritaprevir can be decreased when combined with Clemastine.Approved
ClotrimazoleThe metabolism of Paritaprevir can be decreased when combined with Clotrimazole.Approved, Vet Approved
CobicistatThe metabolism of Paritaprevir can be decreased when combined with Cobicistat.Approved
ConivaptanThe serum concentration of Paritaprevir can be increased when it is combined with Conivaptan.Approved, Investigational
CrizotinibThe metabolism of Paritaprevir can be decreased when combined with Crizotinib.Approved
CyclosporineThe serum concentration of Cyclosporine can be increased when it is combined with Paritaprevir.Approved, Investigational, Vet Approved
DabrafenibThe serum concentration of Paritaprevir can be decreased when it is combined with Dabrafenib.Approved
DasatinibThe serum concentration of Paritaprevir can be increased when it is combined with Dasatinib.Approved, Investigational
DeferasiroxThe serum concentration of Paritaprevir can be decreased when it is combined with Deferasirox.Approved, Investigational
DelavirdineThe metabolism of Paritaprevir can be decreased when combined with Delavirdine.Approved
DigoxinThe serum concentration of Digoxin can be increased when it is combined with Paritaprevir.Approved
DihydroergotamineThe metabolism of Paritaprevir can be decreased when combined with Dihydroergotamine.Approved
DiltiazemThe metabolism of Paritaprevir can be decreased when combined with Diltiazem.Approved
DoxycyclineThe metabolism of Paritaprevir can be decreased when combined with Doxycycline.Approved, Investigational, Vet Approved
DronedaroneThe metabolism of Paritaprevir can be decreased when combined with Dronedarone.Approved
EnzalutamideThe serum concentration of Paritaprevir can be decreased when it is combined with Enzalutamide.Approved
ErythromycinThe metabolism of Paritaprevir can be decreased when combined with Erythromycin.Approved, Vet Approved
FentanylThe serum concentration of Fentanyl can be increased when it is combined with Paritaprevir.Approved, Illicit, Investigational, Vet Approved
FluconazoleThe metabolism of Paritaprevir can be decreased when combined with Fluconazole.Approved
FluvastatinThe serum concentration of Fluvastatin can be increased when it is combined with Paritaprevir.Approved
FluvoxamineThe metabolism of Paritaprevir can be decreased when combined with Fluvoxamine.Approved, Investigational
FosamprenavirThe metabolism of Paritaprevir can be decreased when combined with Fosamprenavir.Approved
FosaprepitantThe serum concentration of Paritaprevir can be increased when it is combined with Fosaprepitant.Approved
FosphenytoinThe metabolism of Paritaprevir can be increased when combined with Fosphenytoin.Approved
Fusidic AcidThe serum concentration of Paritaprevir can be increased when it is combined with Fusidic Acid.Approved
IdelalisibThe serum concentration of Paritaprevir can be increased when it is combined with Idelalisib.Approved
ImatinibThe metabolism of Paritaprevir can be decreased when combined with Imatinib.Approved
IndinavirThe metabolism of Paritaprevir can be decreased when combined with Indinavir.Approved
IsavuconazoniumThe metabolism of Paritaprevir can be decreased when combined with Isavuconazonium.Approved, Investigational
IsradipineThe metabolism of Paritaprevir can be decreased when combined with Isradipine.Approved
ItraconazoleThe metabolism of Paritaprevir can be decreased when combined with Itraconazole.Approved, Investigational
IvacaftorThe serum concentration of Paritaprevir can be increased when it is combined with Ivacaftor.Approved
KetoconazoleThe metabolism of Paritaprevir can be decreased when combined with Ketoconazole.Approved, Investigational
LopinavirThe metabolism of Paritaprevir can be decreased when combined with Lopinavir.Approved
LovastatinThe metabolism of Paritaprevir can be decreased when combined with Lovastatin.Approved, Investigational
LuliconazoleThe serum concentration of Paritaprevir can be increased when it is combined with Luliconazole.Approved
LumacaftorThe metabolism of Paritaprevir can be increased when combined with Lumacaftor.Approved
MifepristoneThe serum concentration of Paritaprevir can be increased when it is combined with Mifepristone.Approved, Investigational
MitotaneThe serum concentration of Paritaprevir can be decreased when it is combined with Mitotane.Approved
NefazodoneThe metabolism of Paritaprevir can be decreased when combined with Nefazodone.Approved, Withdrawn
NelfinavirThe metabolism of Paritaprevir can be decreased when combined with Nelfinavir.Approved
NetupitantThe serum concentration of Paritaprevir can be increased when it is combined with Netupitant.Approved
NevirapineThe metabolism of Paritaprevir can be increased when combined with Nevirapine.Approved
NilotinibThe metabolism of Paritaprevir can be decreased when combined with Nilotinib.Approved, Investigational
OlaparibThe metabolism of Paritaprevir can be decreased when combined with Olaparib.Approved
OsimertinibThe serum concentration of Paritaprevir can be increased when it is combined with Osimertinib.Approved
PalbociclibThe serum concentration of Paritaprevir can be increased when it is combined with Palbociclib.Approved
PentobarbitalThe metabolism of Paritaprevir can be increased when combined with Pentobarbital.Approved, Vet Approved
PhenobarbitalThe metabolism of Paritaprevir can be increased when combined with Phenobarbital.Approved
PhenytoinThe metabolism of Paritaprevir can be increased when combined with Phenytoin.Approved, Vet Approved
PitavastatinThe serum concentration of Pitavastatin can be increased when it is combined with Paritaprevir.Approved
PosaconazoleThe metabolism of Paritaprevir can be decreased when combined with Posaconazole.Approved, Investigational, Vet Approved
PrimidoneThe metabolism of Paritaprevir can be increased when combined with Primidone.Approved, Vet Approved
QuinidineThe serum concentration of Quinidine can be increased when it is combined with Paritaprevir.Approved
RanolazineThe metabolism of Paritaprevir can be decreased when combined with Ranolazine.Approved, Investigational
RifabutinThe metabolism of Paritaprevir can be increased when combined with Rifabutin.Approved
RifampicinThe metabolism of Paritaprevir can be increased when combined with Rifampicin.Approved
RifapentineThe metabolism of Paritaprevir can be increased when combined with Rifapentine.Approved
RitonavirThe metabolism of Paritaprevir can be decreased when combined with Ritonavir.Approved, Investigational
RosuvastatinThe serum concentration of Rosuvastatin can be increased when it is combined with Paritaprevir.Approved
SaquinavirThe metabolism of Paritaprevir can be decreased when combined with Saquinavir.Approved, Investigational
SecobarbitalThe serum concentration of Paritaprevir can be decreased when it is combined with Secobarbital.Approved, Vet Approved
SildenafilThe metabolism of Paritaprevir can be decreased when combined with Sildenafil.Approved, Investigational
SiltuximabThe serum concentration of Paritaprevir can be decreased when it is combined with Siltuximab.Approved
SimeprevirThe serum concentration of Paritaprevir can be increased when it is combined with Simeprevir.Approved
SirolimusThe serum concentration of Sirolimus can be increased when it is combined with Paritaprevir.Approved, Investigational
St. John's WortThe serum concentration of Paritaprevir can be decreased when it is combined with St. John's Wort.Investigational, Nutraceutical
StiripentolThe serum concentration of Paritaprevir can be increased when it is combined with Stiripentol.Approved
SulfisoxazoleThe metabolism of Paritaprevir can be decreased when combined with Sulfisoxazole.Approved, Vet Approved
TacrolimusThe serum concentration of Tacrolimus can be increased when it is combined with Paritaprevir.Approved, Investigational
TelaprevirThe metabolism of Paritaprevir can be decreased when combined with Telaprevir.Approved, Withdrawn
TelithromycinThe metabolism of Paritaprevir can be decreased when combined with Telithromycin.Approved
TiclopidineThe metabolism of Paritaprevir can be decreased when combined with Ticlopidine.Approved
TocilizumabThe serum concentration of Paritaprevir can be decreased when it is combined with Tocilizumab.Approved
VenlafaxineThe metabolism of Paritaprevir can be decreased when combined with Venlafaxine.Approved
VerapamilThe metabolism of Paritaprevir can be decreased when combined with Verapamil.Approved
VoriconazoleThe metabolism of Paritaprevir can be decreased when combined with Voriconazole.Approved, Investigational
ZiprasidoneThe metabolism of Paritaprevir can be decreased when combined with Ziprasidone.Approved
Food Interactions
Not Available

References

General References
  1. Klibanov OM, Gale SE, Santevecchi B: Ombitasvir/paritaprevir/ritonavir and dasabuvir tablets for hepatitis C virus genotype 1 infection. Ann Pharmacother. 2015 May;49(5):566-81. doi: 10.1177/1060028015570729. Epub 2015 Feb 13. [PubMed:25680759]
  2. Hull MW, Yoshida EM, Montaner JS: Update on Current Evidence for Hepatitis C Therapeutic Options in HCV Mono-infected Patients. Curr Infect Dis Rep. 2016 Jul;18(7):22. doi: 10.1007/s11908-016-0527-8. [PubMed:27357277]
  3. Lam JT, Salazar L: New combination antiviral for the treatment of hepatitis C. Am J Health Syst Pharm. 2016 Jul 15;73(14):1042-50. doi: 10.2146/ajhp150163. Epub 2016 May 23. [PubMed:27217519]
  4. 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]
  5. Dusheiko G: Side effects of alpha interferon in chronic hepatitis C. Hepatology. 1997 Sep;26(3 Suppl 1):112S-121S. [PubMed:9305675]
  6. Moradpour D, Penin F: Hepatitis C virus proteins: from structure to function. Curr Top Microbiol Immunol. 2013;369:113-42. doi: 10.1007/978-3-642-27340-7_5. [PubMed:23463199]
  7. 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]
  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
D10580
PubChem Compound
68498031
PubChem Substance
310265189
ChemSpider
34999598
ChEBI
85188
ChEMBL
CHEMBL3391662
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Paritaprevir
ATC Codes
J05AX67 — Ombitasvir, paritaprevir and ritonavirJ05AX66 — Dasabuvir, ombitasvir, paritaprevir and ritonavir
FDA label
Download (6.48 MB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedNot AvailableAbsolute Bioavailability1
1CompletedNot AvailableHealthy Volunteers1
1CompletedTreatmentHCV Infections3
1CompletedTreatmentHealthy Volunteers1
2Active Not RecruitingTreatmentChronic Hepatitis C Virus (HCV) Infection / Hepatitis C (HCV) / Hepatitis C Genotype 11
2CompletedTreatmentChronic Hepatitis C Infection3
2CompletedTreatmentChronic Hepatitis C Infection / Chronic Hepatitis C Virus (HCV) Infection1
2CompletedTreatmentChronic Hepatitis C Infection / HCV / Hepatitis C Genotype 12
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 / Hepatitis C Virus (HCV)1
2CompletedTreatmentChronic Hepatitis C Virus (HCV) Infection / Compensated liver disease / Hepatitis C Virus (HCV)1
2CompletedTreatmentChronic Hepatitis C Virus Infection1
2CompletedTreatmentHepatitis C Virus (HCV)1
2CompletedTreatmentHepatitis C, Chronic1
2RecruitingTreatmentChronic Hepatitis C Virus (HCV) Infection1
2RecruitingTreatmentHuman Immunodeficiency Virus (HIV) Infections1
2, 3RecruitingTreatmentChronic Hepatitis C Infection / HBV Coinfection / Hepatitis B Reactivation1
3Active Not RecruitingTreatmentChronic Hepatitis C Genotype 12
3Active Not RecruitingTreatmentHepatitis C, Acute1
3CompletedOtherChronic Hepatitis C Infection1
3CompletedTreatmentChronic Hepatitis C Infection10
3CompletedTreatmentChronic Hepatitis C Infection / Chronic Hepatitis C Virus (HCV) Infection1
3CompletedTreatmentChronic Hepatitis C Infection / Chronic Kidney Disease (CKD) / Genotype 1a / Genotype 4 / 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 Cirrhosis and Non-cirrhotics / Hepatitis C Virus Infection / Human Immunodeficiency Virus (HIV) Infections1
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)2
3CompletedTreatmentHepatitis C Infection / Hepatitis C Virus (HCV)1
3CompletedTreatmentHepatitis C Virus (HCV)2
3RecruitingTreatmentChronic Hepatitis C Infection1
3WithdrawnTreatmentChronic Hepatitis C Virus1
4Active Not RecruitingTreatmentHepatitis C Virus (HCV)1
4Active Not RecruitingTreatmentHepatitis C, Chronic1
4Not Yet RecruitingTreatmentAntiviral Drug Adverse Reaction1
4RecruitingTreatmentChronic Hepatitis C Virus (HCV) Infection1
4RecruitingTreatmentHCV Coinfection1
Not AvailableActive Not RecruitingNot AvailableChronic Hepatitis C Virus (HCV) Infection / Liver Cirrhosis1
Not AvailableRecruitingNot AvailableHepatitis C, Chronic / Human Immunodeficiency Virus (HIV)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
Kit; tabletOral
Kit
TabletOral
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 Solubility0.00778 mg/mLALOGPS
logP3.5ALOGPS
logP2.49ChemAxon
logS-5ALOGPS
pKa (Strongest Acidic)3.8ChemAxon
pKa (Strongest Basic)2.64ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count10ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area189.65 Å2ChemAxon
Rotatable Bond Count6ChemAxon
Refractivity200.98 m3·mol-1ChemAxon
Polarizability79.7 Å3ChemAxon
Number of Rings8ChemAxon
Bioavailability1ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
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 cyclic peptides. These are compounds containing a cyclic moiety bearing a peptide backbone.
Kingdom
Organic compounds
Super Class
Organic acids and derivatives
Class
Carboxylic acids and derivatives
Sub Class
Amino acids, peptides, and analogues
Direct Parent
Cyclic peptides
Alternative Parents
Phenanthridines and derivatives / Macrolactams / N-acyl-alpha amino acids and derivatives / Alpha amino acid amides / Quinolones and derivatives / Isoquinolines and derivatives / Pyrazinecarboxamides / 2-heteroaryl carboxamides / Alkyl aryl ethers / Pyridines and derivatives
show 15 more
Substituents
Cyclic alpha peptide / Benzoquinoline / Phenanthridine / Macrolactam / N-acyl-alpha amino acid or derivatives / Alpha-amino acid amide / Quinolone / Alpha-amino acid or derivatives / Isoquinoline / Quinoline
show 31 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
aromatic ether, pyrazines, sulfonamide, phenanthridines, lactam, cyclopropanes, aromatic amide, azamacrocycle, carboxamide (CHEBI:85188)

Targets

Kind
Protein
Organism
Hepatitis C virus
Pharmacological action
Yes
Actions
Inhibitor
General Function
Serine-type peptidase activity
Specific Function
Not Available
Gene Name
NS3/4A
Uniprot ID
B0B3C9
Uniprot Name
Genome polyprotein
Molecular Weight
72789.28 Da
References
  1. Lam JT, Salazar L: New combination antiviral for the treatment of hepatitis C. Am J Health Syst Pharm. 2016 Jul 15;73(14):1042-50. doi: 10.2146/ajhp150163. Epub 2016 May 23. [PubMed:27217519]

Enzymes

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, Zhang X, Marsh K, Khatri A, Menon R, Kavetskaia O, Fischer V: Metabolism and Disposition of the Hepatitis C Protease Inhibitor Paritaprevir in Humans. Drug Metab Dispos. 2016 Aug;44(8):1164-73. doi: 10.1124/dmd.115.067488. Epub 2016 May 13. [PubMed:27179127]
Kind
Protein
Organism
Human
Pharmacological action
No
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. Shen J, Serby M, Reed A, Lee AJ, Zhang X, Marsh K, Khatri A, Menon R, Kavetskaia O, Fischer V: Metabolism and Disposition of the Hepatitis C Protease Inhibitor Paritaprevir in Humans. Drug Metab Dispos. 2016 Aug;44(8):1164-73. doi: 10.1124/dmd.115.067488. Epub 2016 May 13. [PubMed:27179127]

Drug created on October 30, 2015 10:02 / Updated on November 09, 2017 04:49