Details
Stereochemistry | ABSOLUTE |
Molecular Formula | C27H37N3O7S.C2H6O |
Molecular Weight | 593.732 |
Optical Activity | UNSPECIFIED |
Defined Stereocenters | 5 / 5 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
CCO.CC(C)CN(C[C@@H](O)[C@H](CC1=CC=CC=C1)NC(=O)O[C@H]2CO[C@H]3OCC[C@@H]23)S(=O)(=O)C4=CC=C(N)C=C4
InChI
InChIKey=QWSHKNICRJHQCY-VBTXLZOXSA-N
InChI=1S/C27H37N3O7S.C2H6O/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;1-2-3/h3-11,18,22-26,31H,12-17,28H2,1-2H3,(H,29,32);3H,2H2,1H3/t22-,23-,24+,25-,26+;/m0./s1
Molecular Formula | C2H6O |
Molecular Weight | 46.0684 |
Charge | 0 |
Count |
|
Stereochemistry | ACHIRAL |
Additional Stereochemistry | No |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Optical Activity | NONE |
Molecular Formula | C27H37N3O7S |
Molecular Weight | 547.664 |
Charge | 0 |
Count |
|
Stereochemistry | ABSOLUTE |
Additional Stereochemistry | No |
Defined Stereocenters | 5 / 5 |
E/Z Centers | 0 |
Optical Activity | UNSPECIFIED |
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 |
---|---|---|---|---|
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 |
|
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 |
|
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 Sources: |
unhealthy, 43 |
Disc. AE: Headache, Gastrointestinal disorder NOS... AEs leading to discontinuation/dose reduction: Headache (grade 3, 0.79%) Sources: Gastrointestinal disorder NOS (5.51%) |
3200 mg single, oral Overdose Dose: 3200 mg Route: oral Route: single Dose: 3200 mg Sources: |
healthy Health Status: healthy Sources: |
|
800 mg 1 times / day multiple, oral Recommended Dose: 800 mg, 1 times / day Route: oral Route: multiple Dose: 800 mg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Disc. AE: Drug-induced hepatitis, Hepatitis acute... AEs leading to discontinuation/dose reduction: Drug-induced hepatitis Sources: Hepatitis 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 Sources: |
unhealthy Health Status: unhealthy Sources: |
Disc. AE: Rash... AEs leading to discontinuation/dose reduction: Rash (grade 1-2, 0.5%) Sources: |
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 Sources: |
unhealthy, 43 |
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 Sources: |
unhealthy, 43 |
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 Sources: |
unhealthy Health Status: unhealthy Sources: |
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 Sources: |
unhealthy Health Status: unhealthy Sources: |
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 Sources: |
unhealthy Health Status: unhealthy Sources: |
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 Sources: |
unhealthy Health Status: unhealthy Sources: |
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 Sources: |
unhealthy Health Status: unhealthy Sources: |
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 Sources: |
unhealthy Health Status: unhealthy Sources: |
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 Sources: |
unhealthy Health Status: unhealthy Sources: |
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 Sources: |
unhealthy Health Status: unhealthy Sources: |
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 Sources: |
unhealthy Health Status: unhealthy Sources: |
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 Sources: |
unhealthy Health Status: unhealthy Sources: |
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 Sources: |
unhealthy Health Status: unhealthy Sources: |
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 Sources: |
unhealthy Health Status: unhealthy Sources: |
PubMed
Title | Date | PubMed |
---|---|---|
Novel bis-tetrahydrofuranylurethane-containing nonpeptidic protease inhibitor (PI) UIC-94017 (TMC114) with potent activity against multi-PI-resistant human immunodeficiency virus in vitro. | 2003 Oct |
|
[New drugs--hope for salvage patients?]. | 2005 Apr 25 |
|
[Protease inhibitors]. | 2005 Dec |
|
Stereoselective and efficient synthesis of (3R,3aS,6aR)-hexahydrofuro[2,3-b]furan-3-ol. | 2005 Dec 22 |
|
A lame duck, a dark horse, and a goat. | 2005 May-Jun |
|
Molecular basis for substrate recognition and drug resistance from 1.1 to 1.6 angstroms resolution crystal structures of HIV-1 protease mutants with substrate analogs. | 2005 Oct |
|
Report from the 13th retrovirus conference. New data on TMC114 and TMC125. | 2006 Apr |
|
Ultra-potent P1 modified arylsulfonamide HIV protease inhibitors: the discovery of GW0385. | 2006 Apr 1 |
|
Anti-HIV agents. Darunavir shows its strength. | 2006 Aug-Sep |
|
Effectiveness of nonpeptide clinical inhibitor TMC-114 on HIV-1 protease with highly drug resistant mutations D30N, I50V, and L90M. | 2006 Feb 23 |
|
FDA approves new PI. | 2006 Jun |
|
Drug interactions. Interactions with TMC114 and TMC125. | 2006 Jun-Jul |
|
New HIV treatment. | 2006 Sep-Oct |
|
Clinical pharmacokinetics of darunavir. | 2007 |
|
Pharmacokinetics of darunavir/ritonavir and TMC125 alone and coadministered in HIV-negative volunteers. | 2007 |
|
Pharmacokinetic interaction between TMC114/r and efavirenz in healthy volunteers. | 2007 |
|
Fast and simultaneous determination of darunavir and eleven other antiretroviral drugs for therapeutic drug monitoring: method development and validation for the determination of all currently approved HIV protease inhibitors and non-nucleoside reverse transcriptase inhibitors in human plasma by liquid chromatography coupled with electrospray ionization tandem mass spectrometry. | 2007 |
|
Pharmacokinetics of darunavir (TMC114) and atazanavir during coadministration in HIV-negative, healthy volunteers. | 2007 |
|
Antiretroviral treatment of HIV infection: Swedish recommendations 2007. | 2007 |
|
AIDS in the Third World: how to stop the HIV infection? | 2007 |
|
Atomic resolution crystal structures of HIV-1 protease and mutants V82A and I84V with saquinavir. | 2007 Apr 1 |
|
Darunavir (TMC114): a new HIV-1 protease inhibitor. | 2007 Aug |
|
Darunavir: a second-generation protease inhibitor. | 2007 Aug 1 |
|
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 |
|
Darunavir (TMC114) approved by the FDA. | 2007 Feb |
|
Efficacy and safety of TMC114/ritonavir in treatment-experienced HIV patients: 24-week results of POWER 1. | 2007 Feb 19 |
|
A novel substrate-based HIV-1 protease inhibitor drug resistance mechanism. | 2007 Jan |
|
Pharmacokinetics and antiretroviral response to darunavir/ritonavir and etravirine combination in patients with high-level viral resistance. | 2007 Jul 11 |
|
Safety, tolerability, and efficacy of darunavir (TMC114) with low-dose ritonavir in treatment-experienced, hepatitis B or C co-infected patients in POWER 1 and 3. | 2007 Jul-Aug |
|
A novel bis-tetrahydrofuranylurethane-containing nonpeptidic protease inhibitor (PI), GRL-98065, is potent against multiple-PI-resistant human immunodeficiency virus in vitro. | 2007 Jun |
|
Prediction of clinical benefits of ritonavir-boosted TMC114 from treatment effects on CD4 counts and HIV RNA. | 2007 May |
|
Prevalence of darunavir resistance mutations in HIV-1-infected patients failing other protease inhibitors. | 2007 Oct |
|
Quantification of darunavir (TMC114) in human plasma by high-performance liquid chromatography with ultra-violet detection. | 2007 Oct 1 |
|
Predicting HIV care costs using CD4 counts from clinical trials. | 2007 Sep |
|
Lessons Learned From 2 Patients With Multidrug-Resistant HIV-1 Infection Successfully Treated With a Darunavir-Containing Antiretroviral Treatment Regimen. | 2007 Sep |
|
Tipranavir: a new option for the treatment of drug-resistant HIV infection. | 2007 Sep 15 |
|
Potent new antiviral compound shows similar inhibition and structural interactions with drug resistant mutants and wild type HIV-1 protease. | 2007 Sep 6 |
|
Design of HIV protease inhibitors targeting protein backbone: an effective strategy for combating drug resistance. | 2008 Jan |
|
Quality control of protease inhibitors. | 2008 Jun |
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.
Substance Class |
Chemical
Created
by
admin
on
Edited
Mon Mar 31 18:08:25 GMT 2025
by
admin
on
Mon Mar 31 18:08:25 GMT 2025
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Record UNII |
33O78XF0BW
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Record Status |
Validated (UNII)
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Record Version |
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EMA ASSESSMENT REPORTS |
REZOLSTA (AUTHORIZED: HIV INFECTIONS)
Created by
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NCI_THESAURUS |
C783
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EMA ASSESSMENT REPORTS |
PREZISTA (AUTHORIZED: HIV INFECTIONS)
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m4099
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644682
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33O78XF0BW
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SUB23573
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100000091852
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CHEMBL1323
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635728-49-3
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C77389
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