Identification

Name
Darunavir
Accession Number
DB01264
Description

Darunavir is a protease inhibitor used with other HIV protease inhibitor drugs as well as ritonavir for the effective management of HIV-1 infection.17 As a second-generation protease inhibitor, darunavir is designed to combat resistance to standard HIV therapy.2,5 It was initially approved by the FDA in 2006.17

Darunavir is being studied as a possible treatment for SARS-CoV-2, the coronavirus responsible for COVID-19, due to in vitro evidence supporting its ability to combat this infection.14 Clinical trials are underway and are expected to conclude in August 2020.19

Type
Small Molecule
Groups
Approved
Structure
Thumb
Weight
Average: 547.664
Monoisotopic: 547.235221243
Chemical Formula
C27H37N3O7S
Synonyms
  • (3R,3aS,6aR)-hexahydrofuro[2,3-b]furan-3-yl N-((1S,2R)-1-benzyl-2-hydroxy-3-(N1-isobutylsulfanilamido)propyl)carbamate
  • (3R,3aS,6aR)-tetrahydro-2H-furo[2,3-b]furan-3-yl (2S,3R)-4-(4-amino-N-isobutylphenylsulfonamido)-3-hydroxy-1-phenylbutan-2-ylcarbamate
  • (3R,3aS,6aR)-tetrahydro-2H-furo[2,3-b]furan-3-yl (2S,3R)-4-(4-amino-N-neopentylphenylsulfonamido)-3-hydroxy-1-phenylbutan-2-ylcarbamate
  • [(S)-3-[(4-Amino-benzenesulfonyl)-isobutyl-amino]-2-hydroxy-1-((R)-phenylmethyl)-propyl]-carbamic acid (3R,3aS,6aR)-(hexahydro-furo[2,3-b]furan-3-yl) ester
  • {(1S,2R)-3-[(4-Amino-benzenesulfonyl)-isobutyl-amino]-1-benzyl-2-hydroxy-propyl}-carbamic acid (3R,3aS,6aR)-(hexahydro-furo[2,3-b]furan-3-yl) ester
  • Darunavir
  • Darunavirum
  • N-((1S,2R)-3-(((4-aminophenyl)sulfonyl)(2-methylpropyl)amino)-2-hydroxy-1-benzylpropyl)((1S,2R,5R)-4,6-dioxabicyclo(3.3.0)oct-2-yloxy)carboxamide
External IDs
  • AIDS073035
  • TMC 114
  • TMC 41629
  • TMC-114
  • TMC-41629
  • TMC114
  • TMC41629
  • UIC 94017
  • UIC-94017

Pharmacology

Indication

Darunavir, co-administered with ritonavir, and with other antiretroviral agents, is indicated for the treatment of human immunodeficiency virus (HIV) in children age 3 or above and adults with HIV-1 infection.17

Associated Conditions
Contraindications & Blackbox Warnings
Learn about our commercial Contraindications & Blackbox Warnings data.
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Pharmacodynamics

Darunavir is an inhibitor of the human immunodeficiency virus (HIV) protease, which prevents HIV viral replication.17 When administered with ritonavir in combination antiretroviral therapy, darunavir significantly decreases viral load and increases CD4 cell counts, decreasing the morbidity and mortality of HIV infection.2,5,8

Mechanism of action

The HIV-1 protease enzyme is necessary for viral precursor protein processing and viral maturation in preparation for infection, and is therefore a target for antiretroviral therapy for HIV. Protease inhibitors are used as a part of highly active antiretroviral therapy (HAART) in patients diagnosed with HIV infection. It has been shown to effectively suppress the virus, leading to significantly decreased morbidity and mortality rates.5

Darunavir, a HIV protease inhibitor, prevents HIV replication through binding to the enzyme, stopping the dimerization and the catalytic activity of HIV-1 protease. In particular, it inhibits the cleavage of HIV encoded Gag-Pol proteins12 in cells that have been infected with the virus, halting the formation of mature virus particles, which spread the infection. The close contact that darunavir makes with the primary chains of the active site amino acids (Asp-29 and Asp-30) on the protease likely contributes to its potency and efficacy against resistant variants of HIV-1.5

Darunavir is known to bind to different sites on the enzyme: the active site cavity and the surface of one of the flexible flaps in the protease dimer. Darunavir can adapt to changes in the shape of a protease enzyme due to its molecular flexibility.5,9

TargetActionsOrganism
AHuman immunodeficiency virus type 1 protease
inhibitor
Human immunodeficiency virus 1
Absorption

The absolute oral bioavailability of one single 600 mg dose of darunavir alone and with 100 mg of ritonavir twice a day was 37% and 82%, respectively.15 Exposure to darunavir in boosted patients has been found to be 11 times higher than in unboosted patients.7 Tmax is achieved approximately 2.4 to 4 hours after oral administration.15,17

When darunavir is taken with food, the Cmax and AUC of darunavir given with ritonavir increase by 30% when compared to the fasted state.15

Volume of distribution

The volume of distribution of darunavir in one pharmacokinetic study in conjunction with ritonavir was 206.5 L (with a range of 161.0–264.9) in healthy young adult volunteers.10 Another pharmacokinetic study revealed a volume of distribution of 220 L.11

Protein binding

Darunavir is approximately 95% bound to plasma proteins. Darunavir binds primarily to plasma alpha 1-acid glycoprotein (AAG).7,15,17

Metabolism

Darunavir is heavily oxidized and metabolized by hepatic cytochrome enzymes, mainly CYP3A.17 Darunavir is extensively metabolized in subjects who do not receive a booster, primarily via carbamate hydrolysis, isobutyl aliphatic hydroxylation, and aniline aromatic hydroxylation, as well as both benzylic aromatic hydroxylation and glucuronidation.7

Route of elimination

A mass balance study in healthy volunteers demonstrated that after single dose administration of 400 mg 14C-darunavir, given with 100 mg ritonavir, approximately 79.5% and 13.9% of the administered dose of radiolabeled darunavir was obtained in the feces and urine, respectively. Excretion of unchanged drug accounted for 8.0% of the darunavir dose in volunteers who were unboosted.7

In boosted darunavir administration, unchanged darunavir made up 48.8% of the excreted dose in boosted subjects due to inhibition of darunavir metabolism by ritonavir. Unchanged drug in the urine made up 1.2% of the administered dose in volunteers who where unboosted, and 7.7% in boosted volunteers.7

Half-life

The terminal elimination half-life of darunavir is approximately 15 hours when it is combined with ritonavir.1,17

Clearance

Darunavir has a low renal clearance.7 After intravenous administration, the clearance darunavir administered alone and with 100 mg ritonavir twice daily, was 32.8 L/h and 5.9 L/h, respectively.17

Adverse Effects
Learn about our commercial Adverse Effects data.
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Toxicity

LD50 information for darunavir is not readily available in the literature.13 One-time doses of up to 3,200 mg of darunavir in an oral solution and up to 1,600 mg of the tablet formulation of darunavir with ritonavir have been given volunteers without significant symptoms.18

Information about an overdose with darunavir with ritonavir is limited. No specific antidote exists for this drug. Treatment of In the case of an overdose, employ general supportive measures. Monitor vital signs and clinical status. It is unlikely that darunavir not amenable to removal by dialysis due to its high level of protein binding.17

Affected organisms
  • Human Immunodeficiency Virus
  • SARS-CoV-2
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AbacavirThe serum concentration of Abacavir can be decreased when it is combined with Darunavir.
AbametapirThe serum concentration of Darunavir can be increased when it is combined with Abametapir.
AbemaciclibThe metabolism of Darunavir can be decreased when combined with Abemaciclib.
AbirateroneThe serum concentration of Abiraterone can be increased when it is combined with Darunavir.
AcalabrutinibThe serum concentration of Acalabrutinib can be increased when it is combined with Darunavir.
AcarboseThe therapeutic efficacy of Acarbose can be increased when used in combination with Darunavir.
AcenocoumarolThe serum concentration of Acenocoumarol can be increased when it is combined with Darunavir.
AcetohexamideThe therapeutic efficacy of Acetohexamide can be increased when used in combination with Darunavir.
Adenovirus type 7 vaccine liveThe therapeutic efficacy of Adenovirus type 7 vaccine live can be decreased when used in combination with Darunavir.
AlbendazoleThe metabolism of Darunavir can be decreased when combined with Albendazole.
Additional Data Available
  • Extended Description
    Extended Description

    Extended description of the mechanism of action and particular properties of each drug interaction.

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  • Severity
    Severity

    A severity rating for each drug interaction, from minor to major.

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  • Evidence Level
    Evidence Level

    A rating for the strength of the evidence supporting each drug interaction.

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  • Action
    Action

    An effect category for each drug interaction. Know how this interaction affects the subject drug.

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Food Interactions
  • Take with food. Food increases absorption.

Products

Product Ingredients
IngredientUNIICASInChI Key
Darunavir ethanolate33O78XF0BW635728-49-3QWSHKNICRJHQCY-VBTXLZOXSA-N
Product Images
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
PrezistaTablet800 mgOralJanssen Pharmaceuticals2012-11-09Not applicableCanada flag
PrezistaTablet, film coated400 mg/1OralState of Florida DOH Central Pharmacy2009-07-01Not applicableUS flag
PrezistaTablet, film coated600 mg/1OralA-S Medication Solutions2008-03-08Not applicableUS flag
PrezistaTablet, film coated600 mgOralJanssen Cilag International Nv2007-02-12Not applicableEU flag
PrezistaTablet, film coated75 mg/1OralJanssen Products LP2009-01-14Not applicableUS flag
PrezistaTablet, film coated800 mgOralJanssen Cilag International Nv2007-02-12Not applicableEU flag
PrezistaTablet, film coated800 mg/1OralAvera McKennan Hospital2015-10-052017-05-24US flag
PrezistaTablet600 mgOralJanssen Pharmaceuticals2009-03-17Not applicableCanada flag
PrezistaTablet, film coated300 mg/1OralPhysicians Total Care, Inc.2007-02-022009-10-30US flag
PrezistaTablet, film coated150 mgOralJanssen Cilag International Nv2007-02-12Not applicableEU flag
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Apo-darunavirTabletOralApotex Corporation2020-02-14Not applicableCanada flag
Apo-darunavirTabletOralApotex Corporation2020-02-14Not applicableCanada flag
Auro-darunavirTabletOralAuro Pharma Inc2020-03-18Not applicableCanada flag
Auro-darunavirTabletOralAuro Pharma Inc2020-03-18Not applicableCanada flag
Auro-darunavirTabletOralAuro Pharma IncNot applicableNot applicableCanada flag
Mar-darunavirTabletOralMarcan Pharmaceuticals IncNot applicableNot applicableCanada flag
Mar-darunavirTabletOralMarcan Pharmaceuticals IncNot applicableNot applicableCanada flag
Mar-darunavirTabletOralMarcan Pharmaceuticals IncNot applicableNot applicableCanada flag
Mylan-darunavirTabletOralMylan PharmaceuticalsNot applicableNot applicableCanada flag
Mylan-darunavirTabletOralMylan PharmaceuticalsNot applicableNot applicableCanada flag
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
PrezcobixDarunavir ethanolate (800 mg/1) + Cobicistat (150 mg/1)Tablet, film coatedOralA-S Medication Solutions2015-01-31Not applicableUS flag
PrezcobixDarunavir (800 mg) + Cobicistat (150 mg)TabletOralJanssen Pharmaceuticals2014-08-28Not applicableCanada flag
PrezcobixDarunavir ethanolate (800 mg/1) + Cobicistat (150 mg/1)Tablet, film coatedOralREMEDYREPACK INC.2017-08-282020-05-04US flag
PrezcobixDarunavir ethanolate (800 mg/1) + Cobicistat (150 mg/1)Tablet, film coatedOralJanssen Products LP2015-01-31Not applicableUS flag
PrezcobixDarunavir ethanolate (800 mg/1) + Cobicistat (150 mg/1)Tablet, film coatedOralA-S Medication Solutions2015-01-312018-07-31US flag
RezolstaDarunavir (800 mg) + Cobicistat (150 mg)Tablet, film coatedOralJanssen Cilag International Nv2014-11-19Not applicableEU flag
SymtuzaDarunavir (800 mg/1) + Cobicistat (150 mg/1) + Emtricitabine (200 mg/1) + Tenofovir alafenamide (10 mg/1)Tablet, film coatedOralJanssen Products LP2018-07-17Not applicableUS flag
SymtuzaDarunavir (800 mg) + Cobicistat (150 mg) + Emtricitabine (200 mg) + Tenofovir alafenamide (10 mg)TabletOralJanssen Pharmaceuticals2018-04-25Not applicableCanada flag

Categories

ATC Codes
J05AR14 — Darunavir and cobicistatG01AE10 — Combinations of sulfonamidesJ05AR22 — Emtricitabine, tenofovir alafenamide, darunavir and cobicistatJ05AR26 — Darunavir and ritonavirJ05AE10 — Darunavir
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as aminobenzenesulfonamides. These are organic compounds containing a benzenesulfonamide moiety with an amine group attached to the benzene ring.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Benzene and substituted derivatives
Sub Class
Benzenesulfonamides
Direct Parent
Aminobenzenesulfonamides
Alternative Parents
Phenylbutylamines / Amphetamines and derivatives / Benzenesulfonyl compounds / Aniline and substituted anilines / Furofurans / Organosulfonamides / Tetrahydrofurans / Aminosulfonyl compounds / Carbamate esters / Secondary alcohols
show 8 more
Substituents
Acetal / Alcohol / Amine / Aminobenzenesulfonamide / Aminosulfonyl compound / Amphetamine or derivatives / Aniline or substituted anilines / Aromatic heteropolycyclic compound / Benzenesulfonyl group / Carbamic acid ester
show 21 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
carbamate ester, sulfonamide, furofuran (CHEBI:367163)

Chemical Identifiers

UNII
YO603Y8113
CAS number
206361-99-1
InChI Key
CJBJHOAVZSMMDJ-HEXNFIEUSA-N
InChI
InChI=1S/C27H37N3O7S/c1-18(2)15-30(38(33,34)21-10-8-20(28)9-11-21)16-24(31)23(14-19-6-4-3-5-7-19)29-27(32)37-25-17-36-26-22(25)12-13-35-26/h3-11,18,22-26,31H,12-17,28H2,1-2H3,(H,29,32)/t22-,23-,24+,25-,26+/m0/s1
IUPAC Name
(3R,3aS,6aR)-hexahydrofuro[2,3-b]furan-3-yl N-[(2S,3R)-3-hydroxy-4-[N-(2-methylpropyl)4-aminobenzenesulfonamido]-1-phenylbutan-2-yl]carbamate
SMILES
[H][[email protected]@]12CCO[[email protected]]1([H])OC[[email protected]@H]2OC(=O)N[[email protected]@H](CC1=CC=CC=C1)[[email protected]](O)CN(CC(C)C)S(=O)(=O)C1=CC=C(N)C=C1

References

Synthesis Reference

Agarwal Virendra, Kumar Katariya, Lalit Keshav, Upadhyay Ashish, Rameschandra Pada Ranjit Ravatbhai, Ghetiya Renish Mansukhlal ,Tuvar Sabirhusen Ismalbhai. 2016. Google patents: WO2016193481A1

US05158713
General References
  1. Back D, Sekar V, Hoetelmans RM: Darunavir: pharmacokinetics and drug interactions. Antivir Ther. 2008;13(1):1-13. [PubMed:18389894]
  2. Tremblay CL: Combating HIV resistance - focus on darunavir. Ther Clin Risk Manag. 2008 Aug;4(4):759-66. [PubMed:19209258]
  3. Koh Y, Matsumi S, Das D, Amano M, Davis DA, Li J, Leschenko S, Baldridge A, Shioda T, Yarchoan R, Ghosh AK, Mitsuya H: Potent inhibition of HIV-1 replication by novel non-peptidyl small molecule inhibitors of protease dimerization. J Biol Chem. 2007 Sep 28;282(39):28709-20. Epub 2007 Jul 17. [PubMed:17635930]
  4. Kovalevsky AY, Tie Y, Liu F, Boross PI, Wang YF, Leshchenko S, Ghosh AK, Harrison RW, Weber IT: Effectiveness of nonpeptide clinical inhibitor TMC-114 on HIV-1 protease with highly drug resistant mutations D30N, I50V, and L90M. J Med Chem. 2006 Feb 23;49(4):1379-87. [PubMed:16480273]
  5. De Meyer S, Azijn H, Surleraux D, Jochmans D, Tahri A, Pauwels R, Wigerinck P, de Bethune MP: TMC114, a novel human immunodeficiency virus type 1 protease inhibitor active against protease inhibitor-resistant viruses, including a broad range of clinical isolates. Antimicrob Agents Chemother. 2005 Jun;49(6):2314-21. [PubMed:15917527]
  6. Croteau D, Rossi SS, Best BM, Capparelli E, Ellis RJ, Clifford DB, Collier AC, Gelman BB, Marra CM, McArthur J, McCutchan JA, Morgello S, Simpson DM, Grant I, Letendre S: Darunavir is predominantly unbound to protein in cerebrospinal fluid and concentrations exceed the wild-type HIV-1 median 90% inhibitory concentration. J Antimicrob Chemother. 2013 Mar;68(3):684-9. doi: 10.1093/jac/dks441. Epub 2012 Nov 9. [PubMed:23143899]
  7. Vermeir M, Lachau-Durand S, Mannens G, Cuyckens F, van Hoof B, Raoof A: Absorption, metabolism, and excretion of darunavir, a new protease inhibitor, administered alone and with low-dose ritonavir in healthy subjects. Drug Metab Dispos. 2009 Apr;37(4):809-20. doi: 10.1124/dmd.108.024109. Epub 2009 Jan 8. [PubMed:19131522]
  8. Balayan T, Horvath H, Rutherford GW: Ritonavir-Boosted Darunavir Plus Two Nucleoside Reverse Transcriptase Inhibitors versus Other Regimens for Initial Antiretroviral Therapy for People with HIV Infection: A Systematic Review. AIDS Res Treat. 2017;2017:2345617. doi: 10.1155/2017/2345617. Epub 2017 Sep 26. [PubMed:29082041]
  9. Purohit R, Sethumadhavan R: Structural basis for the resilience of Darunavir (TMC114) resistance major flap mutations of HIV-1 protease. Interdiscip Sci. 2009 Dec;1(4):320-8. doi: 10.1007/s12539-009-0043-8. Epub 2009 Nov 14. [PubMed:20640812]
  10. Larson KB, Cressey TR, Yogev R, Wiznia A, Hazra R, Jean-Philippe P, Graham B, Gonzalez A, Britto P, Carey VJ, Acosta EP: Pharmacokinetics of Once-Daily Darunavir/Ritonavir With and Without Etravirine in Human Immunodeficiency Virus-Infected Children, Adolescents, and Young Adults. J Pediatric Infect Dis Soc. 2016 Jun;5(2):131-7. doi: 10.1093/jpids/piu142. Epub 2015 Jan 28. [PubMed:27199469]
  11. Ter Heine R, Mulder JW, van Gorp EC, Wagenaar JF, Beijnen JH, Huitema AD: Intracellular and plasma steady-state pharmacokinetics of raltegravir, darunavir, etravirine and ritonavir in heavily pre-treated HIV-infected patients. Br J Clin Pharmacol. 2010 May;69(5):475-83. doi: 10.1111/j.1365-2125.2010.03634.x. [PubMed:20573083]
  12. Davis DA, Soule EE, Davidoff KS, Daniels SI, Naiman NE, Yarchoan R: Activity of human immunodeficiency virus type 1 protease inhibitors against the initial autocleavage in Gag-Pol polyprotein processing. Antimicrob Agents Chemother. 2012 Jul;56(7):3620-8. doi: 10.1128/AAC.00055-12. Epub 2012 Apr 16. [PubMed:22508308]
  13. Rakhmanina NY, Neely MN, Capparelli EV: High dose of darunavir in treatment-experienced HIV-infected adolescent results in virologic suppression and improved CD4 cell count. Ther Drug Monit. 2012 Jun;34(3):237-41. doi: 10.1097/FTD.0b013e3182511efe. [PubMed:22549499]
  14. Charlotte Harrison: Coronavirus puts drug repurposing on the fast track Nature.
  15. Christine J Kubin, Scott M Hammer (2010). Infectious diseases (3rd ed.). Mosby.
  16. Link [Link]
  17. FDA Approved Drug Products: Prezista (darunavir) oral tablets/suspension [Link]
  18. Medicines UK: Zentiva 800mg film coated tablets [Link]
  19. Clinicaltrials.gov: Efficacy and Safety of Darunavir and Cobicistat for Treatment of Pneumonia Caused by 2019-nCoV (DACO-nCoV) [Link]
Human Metabolome Database
HMDB0015393
KEGG Drug
D03656
PubChem Compound
213039
PubChem Substance
46506908
ChemSpider
184733
BindingDB
8125
RxNav
460132
ChEBI
367163
ChEMBL
CHEMBL1323
ZINC
ZINC000003955219
Therapeutic Targets Database
DAP001086
PharmGKB
PA163522472
PDBe Ligand
017
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Darunavir
AHFS Codes
  • 08:18.08.08 — HIV Protease Inhibitors
PDB Entries
1t3r / 1t7i / 2f80 / 2f81 / 2f8g / 2hs1 / 2hs2 / 2idw / 2ien / 2ieo
show 60 more
FDA label
Download (281 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4Active Not RecruitingTreatmentHuman Immunodeficiency Virus (HIV) Infections1
4CompletedNot AvailableHealthy Volunteers1
4CompletedNot AvailableHuman Immunodeficiency Virus (HIV) Infections1
4CompletedNot AvailableHuman Immunodeficiency Virus (HIV) Infections / Proteinuria1
4CompletedOtherHealthy Volunteers1
4CompletedOtherHuman Immunodeficiency Virus Type 1 (HIV-1) Infection1
4CompletedTreatmentCardiovascular Heart Disease / Human Immunodeficiency Virus (HIV) Infections1
4CompletedTreatmentHealthy Volunteers1
4CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections13
4CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections / Hyperlipidemias1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • A-S Medication Solutions LLC
  • Centocor Ortho Biotech Inc.
  • Janssen-Ortho Inc.
  • Lake Erie Medical and Surgical Supply
  • Physicians Total Care Inc.
  • Quality Care
  • Remedy Repack
Dosage Forms
FormRouteStrength
PowderNot applicable1 kg/1kg
Tablet, coatedOral400 mg
Tablet800 MG
Tablet, coatedOral300 MG
Tablet, coatedOral867.3 mg
Tablet, coatedOral650 mg
TabletOral
TabletOral
Tablet, coatedOral150 mg
SuspensionOral100 mg
SuspensionOral100 mg/1mL
SuspensionOral100 mg/ml
TabletOral150 mg
TabletOral300 mg
TabletOral400 mg
TabletOral75 mg
TabletOral800 mg
Tablet, film coated300 MG
Tablet, film coatedOral150 mg
Tablet, film coatedOral150 mg/1
Tablet, film coatedOral300 mg/1
Tablet, film coatedOral300 mg
Tablet, film coatedOral400 mg/1
Tablet, film coatedOral400 mg
Tablet, film coatedOral600 mg
Tablet, film coatedOral600 mg/1
Tablet, film coatedOral75 mg/1
Tablet, film coatedOral75 mg
Tablet, film coatedOral800 mg/1
Tablet, film coatedOral800 mg
Tablet, coatedOral75 mg
Tablet, coated150 mg
Tablet, coated400 mg
Tablet, coated600 mg
Tablet
Tablet, coated75 mg
Tablet, film coatedOral
Tablet, coatedOral600 mg
TabletOral600 mg
Tablet, coatedOral800 mg
Prices
Unit descriptionCostUnit
Prezista 600 mg tablet25.75USD tablet
Prezista 400 mg tablet18.74USD tablet
Prezista 300 mg tablet16.2USD tablet
Prezista 150 mg tablet4.59USD tablet
Prezista 75 mg tablet2.3USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US6335460No2002-01-012012-08-25US flag
CA2469343No2008-05-132022-12-12Canada flag
CA2224738No2002-08-272016-06-28Canada flag
US6703403Yes2004-03-092016-12-26US flag
US6037157Yes2000-03-142016-12-26US flag
US6642245Yes2003-11-042021-05-04US flag
US6703396Yes2004-03-092021-09-09US flag
US5843946Yes1998-12-012016-06-01US flag
US7470506Yes2008-12-302019-12-23US flag
USRE43802Yes2012-11-132017-04-19US flag
US8597876Yes2013-12-032019-12-23US flag
US7700645Yes2010-04-202027-06-26US flag
USRE42889Yes2011-11-012017-04-19US flag
US8518987Yes2013-08-272024-08-16US flag
USRE43596Yes2012-08-212017-11-09US flag
US8148374No2012-04-032029-09-03US flag
US9296769No2016-03-292032-08-15US flag
US7803788No2010-09-282022-02-02US flag
US8754065No2014-06-172032-08-15US flag
US7390791No2008-06-242022-05-07US flag
US9889115Yes2018-02-132019-12-23US flag
US10039718No2018-08-072032-10-04US flag
Additional Data Available
  • Filed On
    Filed On

    The date on which a patent was filed with the relevant government.

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Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)74-76https://www.chemicalbook.com/ChemicalProductProperty_EN_CB61121362.htm
water solubilityApproximately 0.15 mg/mL at https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/021976s003s004lbl.pdf
logP1.89http://www.antimicrobe.org/d94.asp
pKa11.43±0.46(Predicted)https://www.chemicalbook.com/ChemicalProductProperty_US_CB51176244.aspx
Predicted Properties
PropertyValueSource
Water Solubility0.0668 mg/mLALOGPS
logP1.76ALOGPS
logP2.82ChemAxon
logS-3.9ALOGPS
pKa (Strongest Acidic)13.59ChemAxon
pKa (Strongest Basic)2.39ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count7ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area140.42 Å2ChemAxon
Rotatable Bond Count11ChemAxon
Refractivity142.34 m3·mol-1ChemAxon
Polarizability57.49 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+0.9636
Blood Brain Barrier-0.5518
Caco-2 permeable+0.7274
P-glycoprotein substrateSubstrate0.7464
P-glycoprotein inhibitor IInhibitor0.7588
P-glycoprotein inhibitor IINon-inhibitor0.8683
Renal organic cation transporterNon-inhibitor0.8847
CYP450 2C9 substrateNon-substrate0.5747
CYP450 2D6 substrateSubstrate0.6809
CYP450 3A4 substrateSubstrate0.6496
CYP450 1A2 substrateNon-inhibitor0.7328
CYP450 2C9 inhibitorNon-inhibitor0.6999
CYP450 2D6 inhibitorNon-inhibitor0.8784
CYP450 2C19 inhibitorNon-inhibitor0.6587
CYP450 3A4 inhibitorNon-inhibitor0.5076
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.7132
Ames testNon AMES toxic0.5933
CarcinogenicityNon-carcinogens0.7991
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.5482 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9824
hERG inhibition (predictor II)Non-inhibitor0.857
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
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
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-0aor-0900800000-e427a102e3a7551cc732
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-0a4i-0900000000-8ab8c2b3421f4a277282
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-0a4i-2900000000-eddacc917eaf16abe9d2
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-0a4i-2900000000-86c785caeafe3b4a10c3
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-0a4l-5900000000-69bc90a59383cb5a804b
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-0a4l-8900000000-f481d0932a99692c87d9
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-000g-0009760000-f730e27547a482694ebc
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0006-0009000000-fcd18a6f4e9084f0f8f1
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0006-0469000000-716a2ae87ad9df6765fb
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0a4i-0941000000-5e0dbe51025009642b33
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0a4i-0910000000-2411514d55bfa3c4e81f
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0006-2309000000-e6767f5d8648334c41c9
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-014i-9621000000-3a7c794f5e3f473b9ad5
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-014i-9400000000-16b363cdd836532460ce
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0a4i-2900000000-98bfa9c688e4cb2dbbc3
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0a4l-4900000000-05c5a10ff111a5d1c9bf
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-052f-6900000000-f59c1c0d97f0a8ab00d7

Targets

Kind
Protein
Organism
Human immunodeficiency virus 1
Pharmacological action
Yes
Actions
Inhibitor
General Function
Aspartic-type endopeptidase activity
Specific Function
Not Available
Gene Name
pol
Uniprot ID
Q72874
Uniprot Name
Pol polyprotein
Molecular Weight
10778.7 Da
References
  1. Dierynck I, De Wit M, Gustin E, Keuleers I, Vandersmissen J, Hallenberger S, Hertogs K: Binding kinetics of darunavir to human immunodeficiency virus type 1 protease explain the potent antiviral activity and high genetic barrier. J Virol. 2007 Dec;81(24):13845-51. Epub 2007 Oct 10. [PubMed:17928344]
  2. Ghosh AK, Dawson ZL, Mitsuya H: Darunavir, a conceptually new HIV-1 protease inhibitor for the treatment of drug-resistant HIV. Bioorg Med Chem. 2007 Dec 15;15(24):7576-80. Epub 2007 Sep 14. [PubMed:17900913]
  3. Wang YF, Tie Y, Boross PI, Tozser J, Ghosh AK, Harrison RW, Weber IT: Potent new antiviral compound shows similar inhibition and structural interactions with drug resistant mutants and wild type HIV-1 protease. J Med Chem. 2007 Sep 6;50(18):4509-15. Epub 2007 Aug 16. [PubMed:17696515]
  4. McKeage K, Perry CM, Keam SJ: Darunavir: a review of its use in the management of HIV infection in adults. Drugs. 2009;69(4):477-503. doi: 10.2165/00003495-200969040-00007. [PubMed:19323590]
  5. Tremblay CL: Combating HIV resistance - focus on darunavir. Ther Clin Risk Manag. 2008 Aug;4(4):759-66. [PubMed:19209258]
  6. Kovalevsky AY, Tie Y, Liu F, Boross PI, Wang YF, Leshchenko S, Ghosh AK, Harrison RW, Weber IT: Effectiveness of nonpeptide clinical inhibitor TMC-114 on HIV-1 protease with highly drug resistant mutations D30N, I50V, and L90M. J Med Chem. 2006 Feb 23;49(4):1379-87. [PubMed:16480273]
  7. De Meyer S, Azijn H, Surleraux D, Jochmans D, Tahri A, Pauwels R, Wigerinck P, de Bethune MP: TMC114, a novel human immunodeficiency virus type 1 protease inhibitor active against protease inhibitor-resistant viruses, including a broad range of clinical isolates. Antimicrob Agents Chemother. 2005 Jun;49(6):2314-21. [PubMed:15917527]
  8. FDA Approved Drug Products: Prezista (darunavir) oral tablets/suspension [Link]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
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...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. McKeage K, Perry CM, Keam SJ: Darunavir: a review of its use in the management of HIV infection in adults. Drugs. 2009;69(4):477-503. doi: 10.2165/00003495-200969040-00007. [PubMed:19323590]
  2. Tremblay CL: Combating HIV resistance - focus on darunavir. Ther Clin Risk Manag. 2008 Aug;4(4):759-66. [PubMed:19209258]
  3. Busse KH, Penzak SR: Darunavir: a second-generation protease inhibitor. Am J Health Syst Pharm. 2007 Aug 1;64(15):1593-602. doi: 10.2146/ajhp060668. [PubMed:17646561]
  4. Brown KC, Paul S, Kashuba AD: Drug interactions with new and investigational antiretrovirals. Clin Pharmacokinet. 2009;48(4):211-41. [PubMed:19492868]
  5. FDA Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers [Link]
  6. FDA Approved Drug Products: Prezista (darunavir) oral tablets/suspension [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
Curator comments
When given with ritonavir, cobicistat inhibits the CYP2D6 enzyme.
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: Prezista (darunavir) oral tablets/suspension [Link]

Carriers

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
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. Croteau D, Rossi SS, Best BM, Capparelli E, Ellis RJ, Clifford DB, Collier AC, Gelman BB, Marra CM, McArthur J, McCutchan JA, Morgello S, Simpson DM, Grant I, Letendre S: Darunavir is predominantly unbound to protein in cerebrospinal fluid and concentrations exceed the wild-type HIV-1 median 90% inhibitory concentration. J Antimicrob Chemother. 2013 Mar;68(3):684-9. doi: 10.1093/jac/dks441. Epub 2012 Nov 9. [PubMed:23143899]
  2. Shi JH, Zhou KL, Lou YY, Pan DQ: Multi-spectroscopic and molecular modeling approaches to elucidate the binding interaction between bovine serum albumin and darunavir, a HIV protease inhibitor. Spectrochim Acta A Mol Biomol Spectrosc. 2018 Jan 5;188:362-371. doi: 10.1016/j.saa.2017.07.040. Epub 2017 Jul 23. [PubMed:28753530]
  3. Yilmaz A, Izadkhashti A, Price RW, Mallon PW, De Meulder M, Timmerman P, Gisslen M: Darunavir concentrations in cerebrospinal fluid and blood in HIV-1-infected individuals. AIDS Res Hum Retroviruses. 2009 Apr;25(4):457-61. doi: 10.1089/aid.2008.0216. [PubMed:19320601]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
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. Croteau D, Rossi SS, Best BM, Capparelli E, Ellis RJ, Clifford DB, Collier AC, Gelman BB, Marra CM, McArthur J, McCutchan JA, Morgello S, Simpson DM, Grant I, Letendre S: Darunavir is predominantly unbound to protein in cerebrospinal fluid and concentrations exceed the wild-type HIV-1 median 90% inhibitory concentration. J Antimicrob Chemother. 2013 Mar;68(3):684-9. doi: 10.1093/jac/dks441. Epub 2012 Nov 9. [PubMed:23143899]
  2. Yilmaz A, Izadkhashti A, Price RW, Mallon PW, De Meulder M, Timmerman P, Gisslen M: Darunavir concentrations in cerebrospinal fluid and blood in HIV-1-infected individuals. AIDS Res Hum Retroviruses. 2009 Apr;25(4):457-61. doi: 10.1089/aid.2008.0216. [PubMed:19320601]

Transporters

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
References
  1. Annaert P, Ye ZW, Stieger B, Augustijns P: Interaction of HIV protease inhibitors with OATP1B1, 1B3, and 2B1. Xenobiotica. 2010 Mar;40(3):163-76. doi: 10.3109/00498250903509375. [PubMed:20102298]
  2. Molto J, Xinarianos G, Miranda C, Pushpakom S, Cedeno S, Clotet B, Owen A, Valle M: Simultaneous pharmacogenetics-based population pharmacokinetic analysis of darunavir and ritonavir in HIV-infected patients. Clin Pharmacokinet. 2013 Jul;52(7):543-53. doi: 10.1007/s40262-013-0057-6. [PubMed:23494984]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
Inducer
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. Tempestilli M, Gentilotti E, Tommasi C, Nicastri E, Martini F, De Nardo P, Narciso P, Pucillo LP: Determination of P-glycoprotein surface expression and functional ability after in vitro treatment with darunavir or raltegravir in lymphocytes of healthy donors. Int Immunopharmacol. 2013 Aug;16(4):492-7. doi: 10.1016/j.intimp.2013.05.003. Epub 2013 May 23. [PubMed:23707228]
  2. Konig SK, Herzog M, Theile D, Zembruski N, Haefeli WE, Weiss J: Impact of drug transporters on cellular resistance towards saquinavir and darunavir. J Antimicrob Chemother. 2010 Nov;65(11):2319-28. doi: 10.1093/jac/dkq324. Epub 2010 Sep 3. [PubMed:20817741]
  3. Chan GN, Patel R, Cummins CL, Bendayan R: Induction of P-glycoprotein by antiretroviral drugs in human brain microvessel endothelial cells. Antimicrob Agents Chemother. 2013 Sep;57(9):4481-8. doi: 10.1128/AAC.00486-13. Epub 2013 Jul 8. [PubMed:23836171]
  4. FDA Approved Drug Products: Prezista (darunavir) oral tablets/suspension [Link]

Drug created on May 16, 2007 11:43 / Updated on October 21, 2020 01:55

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