Details
Stereochemistry | ABSOLUTE |
Molecular Formula | C27H37N3O7S |
Molecular Weight | 547.664 |
Optical Activity | ( - ) |
Defined Stereocenters | 5 / 5 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
[H][C@]12OCC[C@@]1([H])[C@H](CO2)OC(=O)N[C@@H](CC3=CC=CC=C3)[C@H](O)CN(CC(C)C)S(=O)(=O)C4=CC=C(N)C=C4
InChI
InChIKey=CJBJHOAVZSMMDJ-HEXNFIEUSA-N
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
DescriptionCurator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/23708741 | http://adisinsight.springer.com/drugs/800016726
Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/23708741 | http://adisinsight.springer.com/drugs/800016726
Darunavir (trade name Prezista) is an orally active bis-furan-sulfonamide inhibitor of human immunodeficiency virus (HIV-1) protease. Darunavir was developed by Tibotec Pharmaceuticals (now Janssen R&D Ireland). Darunavir is indicated for the treatment of HIV-1 infection in adult and pediatric patients 3 years of age and older. The drug is co-administered with low-dose ritonavir and other anti-HIV agents. It is the only antiretroviral that has been registered at two different doses, 800/100 mg once-daily or 600/100 mg twice-daily, allowing its administration throughout the entire course of HIV disease, from naive subjects without any HIV-1 resistance to heavily treatment-experienced subjects with widespread triple-class family resistance.
Originator
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL243 Sources: https://www.ncbi.nlm.nih.gov/pubmed/15479840 |
4.5 pM [Kd] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | PREZISTA Approved UsePREZISTA is a human immunodeficiency virus (HIV-1) protease inhibitor indicated for the treatment of HIV-1 infection in adult patients. PREZISTA is also indicated for the treatment of HIV-1 infection in pediatric patients 3 years of age and older. PREZISTA must be co-administered with ritonavir (PREZISTA/ritonavir) and with other antiretroviral agents. Launch Date2006 |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
5272 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21926632/ |
800 mg 1 times / day steady-state, oral dose: 800 mg route of administration: Oral experiment type: STEADY-STATE co-administered: Ritonavir |
DARUNAVIR plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
AUC
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
93026 ng × h/mL |
800 mg 1 times / day steady-state, oral dose: 800 mg route of administration: Oral experiment type: STEADY-STATE co-administered: Ritonavir |
DARUNAVIR plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
124698 ng × h/mL |
600 mg 2 times / day steady-state, oral dose: 600 mg route of administration: Oral experiment type: STEADY-STATE co-administered: Ritonavir |
DARUNAVIR plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
57055 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21926632/ |
800 mg 1 times / day steady-state, oral dose: 800 mg route of administration: Oral experiment type: STEADY-STATE co-administered: Ritonavir |
DARUNAVIR plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
126377 ng × h/mL |
600 mg 2 times / day steady-state, oral dose: 600 mg route of administration: Oral experiment type: STEADY-STATE co-administered: Ritonavir |
DARUNAVIR plasma | Homo sapiens population: UNHEALTHY age: CHILD sex: FEMALE / MALE food status: UNKNOWN |
T1/2
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
15 h |
800 mg 1 times / day steady-state, oral dose: 800 mg route of administration: Oral experiment type: STEADY-STATE co-administered: Ritonavir |
DARUNAVIR plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
15 h |
600 mg 2 times / day steady-state, oral dose: 600 mg route of administration: Oral experiment type: STEADY-STATE co-administered: Ritonavir |
DARUNAVIR plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
Funbound
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
5% |
800 mg 1 times / day steady-state, oral dose: 800 mg route of administration: Oral experiment type: STEADY-STATE co-administered: Ritonavir |
DARUNAVIR plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
5% |
600 mg 2 times / day steady-state, oral dose: 600 mg route of administration: Oral experiment type: STEADY-STATE co-administered: Ritonavir |
DARUNAVIR plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
Doses
Dose | Population | Adverse events |
---|---|---|
800 mg 1 times / day multiple, oral Recommended Dose: 800 mg, 1 times / day Route: oral Route: multiple Dose: 800 mg, 1 times / day Co-administed with:: ritonavir, oral(100 mg; qd) Sources: Page: p.227 |
unhealthy, 43 n = 127 Health Status: unhealthy Condition: HIV-1 infection Age Group: 43 Sex: M+F Population Size: 127 Sources: Page: p.227 |
Disc. AE: Headache, Gastrointestinal disorder NOS... AEs leading to discontinuation/dose reduction: Headache (grade 3, 0.79%) Sources: Page: p.227Gastrointestinal disorder NOS (5.51%) |
3200 mg single, oral Overdose Dose: 3200 mg Route: oral Route: single Dose: 3200 mg Sources: Page: p.22 |
healthy Health Status: healthy Sources: Page: p.22 |
|
800 mg 1 times / day multiple, oral Recommended Dose: 800 mg, 1 times / day Route: oral Route: multiple Dose: 800 mg, 1 times / day Co-administed with:: ritonavir, oral(100 mg; qd) Sources: Page: p.1 |
unhealthy Health Status: unhealthy Condition: HIV-1 infection Sources: Page: p.1 |
Disc. AE: Drug-induced hepatitis, Hepatitis acute... AEs leading to discontinuation/dose reduction: Drug-induced hepatitis Sources: Page: p.1Hepatitis acute Cytolytic hepatitis Reaction skin (grade 1-3) Stevens-Johnson syndrome Toxic epidermal necrolysis Diabetes mellitus Hyperglycemia Fat redistribution Fat tissue increased Immune reconstitution syndrome |
800 mg 1 times / day multiple, oral Recommended Dose: 800 mg, 1 times / day Route: oral Route: multiple Dose: 800 mg, 1 times / day Co-administed with:: ritonavir, oral(100 mg; qd) Sources: Page: p.8 |
unhealthy Health Status: unhealthy Condition: HIV-1 infection Sources: Page: p.8 |
Disc. AE: Rash... AEs leading to discontinuation/dose reduction: Rash (grade 1-2, 0.5%) Sources: Page: p.8 |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
Gastrointestinal disorder NOS | 5.51% Disc. AE |
800 mg 1 times / day multiple, oral Recommended Dose: 800 mg, 1 times / day Route: oral Route: multiple Dose: 800 mg, 1 times / day Co-administed with:: ritonavir, oral(100 mg; qd) Sources: Page: p.227 |
unhealthy, 43 n = 127 Health Status: unhealthy Condition: HIV-1 infection Age Group: 43 Sex: M+F Population Size: 127 Sources: Page: p.227 |
Headache | grade 3, 0.79% Disc. AE |
800 mg 1 times / day multiple, oral Recommended Dose: 800 mg, 1 times / day Route: oral Route: multiple Dose: 800 mg, 1 times / day Co-administed with:: ritonavir, oral(100 mg; qd) Sources: Page: p.227 |
unhealthy, 43 n = 127 Health Status: unhealthy Condition: HIV-1 infection Age Group: 43 Sex: M+F Population Size: 127 Sources: Page: p.227 |
Cytolytic hepatitis | Disc. AE | 800 mg 1 times / day multiple, oral Recommended Dose: 800 mg, 1 times / day Route: oral Route: multiple Dose: 800 mg, 1 times / day Co-administed with:: ritonavir, oral(100 mg; qd) Sources: Page: p.1 |
unhealthy Health Status: unhealthy Condition: HIV-1 infection Sources: Page: p.1 |
Diabetes mellitus | Disc. AE | 800 mg 1 times / day multiple, oral Recommended Dose: 800 mg, 1 times / day Route: oral Route: multiple Dose: 800 mg, 1 times / day Co-administed with:: ritonavir, oral(100 mg; qd) Sources: Page: p.1 |
unhealthy Health Status: unhealthy Condition: HIV-1 infection Sources: Page: p.1 |
Drug-induced hepatitis | Disc. AE | 800 mg 1 times / day multiple, oral Recommended Dose: 800 mg, 1 times / day Route: oral Route: multiple Dose: 800 mg, 1 times / day Co-administed with:: ritonavir, oral(100 mg; qd) Sources: Page: p.1 |
unhealthy Health Status: unhealthy Condition: HIV-1 infection Sources: Page: p.1 |
Fat redistribution | Disc. AE | 800 mg 1 times / day multiple, oral Recommended Dose: 800 mg, 1 times / day Route: oral Route: multiple Dose: 800 mg, 1 times / day Co-administed with:: ritonavir, oral(100 mg; qd) Sources: Page: p.1 |
unhealthy Health Status: unhealthy Condition: HIV-1 infection Sources: Page: p.1 |
Fat tissue increased | Disc. AE | 800 mg 1 times / day multiple, oral Recommended Dose: 800 mg, 1 times / day Route: oral Route: multiple Dose: 800 mg, 1 times / day Co-administed with:: ritonavir, oral(100 mg; qd) Sources: Page: p.1 |
unhealthy Health Status: unhealthy Condition: HIV-1 infection Sources: Page: p.1 |
Hepatitis acute | Disc. AE | 800 mg 1 times / day multiple, oral Recommended Dose: 800 mg, 1 times / day Route: oral Route: multiple Dose: 800 mg, 1 times / day Co-administed with:: ritonavir, oral(100 mg; qd) Sources: Page: p.1 |
unhealthy Health Status: unhealthy Condition: HIV-1 infection Sources: Page: p.1 |
Hyperglycemia | Disc. AE | 800 mg 1 times / day multiple, oral Recommended Dose: 800 mg, 1 times / day Route: oral Route: multiple Dose: 800 mg, 1 times / day Co-administed with:: ritonavir, oral(100 mg; qd) Sources: Page: p.1 |
unhealthy Health Status: unhealthy Condition: HIV-1 infection Sources: Page: p.1 |
Immune reconstitution syndrome | Disc. AE | 800 mg 1 times / day multiple, oral Recommended Dose: 800 mg, 1 times / day Route: oral Route: multiple Dose: 800 mg, 1 times / day Co-administed with:: ritonavir, oral(100 mg; qd) Sources: Page: p.1 |
unhealthy Health Status: unhealthy Condition: HIV-1 infection Sources: Page: p.1 |
Stevens-Johnson syndrome | Disc. AE | 800 mg 1 times / day multiple, oral Recommended Dose: 800 mg, 1 times / day Route: oral Route: multiple Dose: 800 mg, 1 times / day Co-administed with:: ritonavir, oral(100 mg; qd) Sources: Page: p.1 |
unhealthy Health Status: unhealthy Condition: HIV-1 infection Sources: Page: p.1 |
Toxic epidermal necrolysis | Disc. AE | 800 mg 1 times / day multiple, oral Recommended Dose: 800 mg, 1 times / day Route: oral Route: multiple Dose: 800 mg, 1 times / day Co-administed with:: ritonavir, oral(100 mg; qd) Sources: Page: p.1 |
unhealthy Health Status: unhealthy Condition: HIV-1 infection Sources: Page: p.1 |
Reaction skin | grade 1-3 Disc. AE |
800 mg 1 times / day multiple, oral Recommended Dose: 800 mg, 1 times / day Route: oral Route: multiple Dose: 800 mg, 1 times / day Co-administed with:: ritonavir, oral(100 mg; qd) Sources: Page: p.1 |
unhealthy Health Status: unhealthy Condition: HIV-1 infection Sources: Page: p.1 |
Rash | grade 1-2, 0.5% Disc. AE |
800 mg 1 times / day multiple, oral Recommended Dose: 800 mg, 1 times / day Route: oral Route: multiple Dose: 800 mg, 1 times / day Co-administed with:: ritonavir, oral(100 mg; qd) Sources: Page: p.8 |
unhealthy Health Status: unhealthy Condition: HIV-1 infection Sources: Page: p.8 |
PubMed
Title | Date | PubMed |
---|---|---|
Stereoselective photochemical 1,3-dioxolane addition to 5-alkoxymethyl-2(5H)-furanone: synthesis of bis-tetrahydrofuranyl ligand for HIV protease inhibitor UIC-94017 (TMC-114). | 2004 Nov 12 |
|
[New drugs--hope for salvage patients?]. | 2005 Apr 25 |
|
Anti-HIV agents. What the future holds for TMC114. | 2005 Aug-Sep |
|
Anti-HIV agents. Interactions with TMC114. | 2005 Aug-Sep |
|
Development of a capillary electrophoretic method for the separation of diastereoisomers of a new human immunodeficiency virus protease inhibitor. | 2005 Feb |
|
New drugs. | 2005 Jul |
|
TMC114, a novel human immunodeficiency virus type 1 protease inhibitor active against protease inhibitor-resistant viruses, including a broad range of clinical isolates. | 2005 Jun |
|
Design of HIV-1 protease inhibitors active on multidrug-resistant virus. | 2005 Mar 24 |
|
New protease inhibitor TMC-114. Preliminary 24-week late breaker results of the phase II trial. | 2005 Mar-Apr |
|
Report from the 13th retrovirus conference. New data on TMC114 and TMC125. | 2006 Apr |
|
Successful rescue therapy with darunabir (TMC114) in HIV-infected patients who have failed several ritonavir-boosted protease inhibitors. | 2006 Jul 13 |
|
FDA approves new PI. | 2006 Jun |
|
The clinical pharmacology of antiretrovirals in development. | 2006 Jun |
|
Drug interactions. Interactions with TMC114 and TMC125. | 2006 Jun-Jul |
|
British HIV Association (BHIVA) guidelines for the treatment of HIV-infected adults with antiretroviral therapy (2006). | 2006 Nov |
|
Darunavir (Prezista) for HIV infection. | 2006 Sep 11 |
|
New HIV treatment. | 2006 Sep-Oct |
|
Atomic resolution crystal structures of HIV-1 protease and mutants V82A and I84V with saquinavir. | 2007 Apr 1 |
|
Development of therapeutics for AIDS: structure-based molecular targeting. | 2007 Aug |
|
Overview of boosted protease inhibitors in treatment-experienced HIV-infected patients. | 2007 Dec |
|
Darunavir, a conceptually new HIV-1 protease inhibitor for the treatment of drug-resistant HIV. | 2007 Dec 15 |
|
Efficacy and safety of TMC114/ritonavir in treatment-experienced HIV patients: 24-week results of POWER 1. | 2007 Feb 19 |
|
Efficacy and safety of darunavir-ritonavir compared with that of lopinavir-ritonavir at 48 weeks in treatment-experienced, HIV-infected patients in TITAN: a randomised controlled phase III trial. | 2007 Jul 7 |
|
Editorial comment: impact of darunavir for salvage therapy. | 2007 Mar |
|
Darunavir: an overview of an HIV protease inhibitor developed to overcome drug resistance. | 2007 Mar |
|
Analysis of treatment costs for HIV RNA reductions and CD4 increases for darunavir versus other antiretrovirals in treatment-experienced, HIV-infected patients. | 2007 May-Jun |
|
Safety and efficacy of darunavir (TMC114) with low-dose ritonavir in treatment-experienced patients: 24-week results of POWER 3. | 2007 Sep 1 |
|
Potent inhibition of HIV-1 replication by novel non-peptidyl small molecule inhibitors of protease dimerization. | 2007 Sep 28 |
|
Potent new antiviral compound shows similar inhibition and structural interactions with drug resistant mutants and wild type HIV-1 protease. | 2007 Sep 6 |
Sample Use Guides
Treatment-naïve adult patients and treatment-experienced adult patients with no darunavir resistance associated substitutions:
800 mg (two 400 mg tablets) taken with ritonavir 100 mg once daily and with food. Treatment-experienced adult patients with at least one darunavir resistance associated substitution: 600 mg (one 600 mg tablet) taken with ritonavir 100 mg twice daily and with food. Pediatric patients (3 to less than 18 years of age and weighing at
least 10 kg): dosage of PREZISTA and ritonavir is based on body weight and should not exceed the treatmentexperienced adult dose. Do not use once daily dosing in pediatric patients. PREZISTA should be taken with ritonavir twice daily and with food.
Route of Administration:
Oral
Darunavir exhibits activity against laboratory strains and clinical isolates of HIV-1 and laboratory strains of HIV-2 in acutely infected T-cell lines, human peripheral blood mononuclear cells and human monocytes/macrophages with median EC50 values ranging from 1.2 to 8.5 nM (0.7 to 5.0 ng/mL). Darunavir demonstrates antiviral activity in cell culture against a broad panel of HIV-1 group M (A, B, C, D, E, F, G), and group O primary isolates with EC50 values ranging from less than 0.1 to 4.3 nM.
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Classification Tree | Code System | Code | ||
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WHO-ATC |
J05AE10
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LIVERTOX |
NBK547994
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NDF-RT |
N0000175889
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WHO-ATC |
J05AR14
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NDF-RT |
N0000000246
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WHO-VATC |
QJ05AE10
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NCI_THESAURUS |
C783
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206361-99-1
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DTXSID0046779
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YO603Y8113
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N0000190114
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PRIMARY | Cytochrome P450 3A Inhibitors [MoA] | ||
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Darunavir
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DARUNAVIR
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8305
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7788
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CHEMBL1323
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YO603Y8113
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RR-31
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m4099
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PRIMARY | Merck Index | ||
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SUB25394
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C65364
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4143
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DB01264
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367163
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100000089367
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460132
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213039
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C482292
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ACTIVE MOIETY
METABOLITE (PARENT)
METABOLITE (PARENT)
METABOLITE (PARENT)
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SALT/SOLVATE (PARENT)
SALT/SOLVATE (PARENT)
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