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 |
|---|---|---|
| Quality control of protease inhibitors. | 2008-06 |
|
| Design of HIV protease inhibitors targeting protein backbone: an effective strategy for combating drug resistance. | 2008-01 |
|
| Darunavir, a conceptually new HIV-1 protease inhibitor for the treatment of drug-resistant HIV. | 2007-12-15 |
|
| Overview of boosted protease inhibitors in treatment-experienced HIV-infected patients. | 2007-12 |
|
| Quantification of darunavir (TMC114) in human plasma by high-performance liquid chromatography with ultra-violet detection. | 2007-10-01 |
|
| Prevalence of darunavir resistance mutations in HIV-1-infected patients failing other protease inhibitors. | 2007-10 |
|
| Potent inhibition of HIV-1 replication by novel non-peptidyl small molecule inhibitors of protease dimerization. | 2007-09-28 |
|
| Tipranavir: a new option for the treatment of drug-resistant HIV infection. | 2007-09-15 |
|
| Potent new antiviral compound shows similar inhibition and structural interactions with drug resistant mutants and wild type HIV-1 protease. | 2007-09-06 |
|
| Safety and efficacy of darunavir (TMC114) with low-dose ritonavir in treatment-experienced patients: 24-week results of POWER 3. | 2007-09-01 |
|
| Predicting HIV care costs using CD4 counts from clinical trials. | 2007-09 |
|
| Lessons Learned From 2 Patients With Multidrug-Resistant HIV-1 Infection Successfully Treated With a Darunavir-Containing Antiretroviral Treatment Regimen. | 2007-09 |
|
| 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. | 2007-08-28 |
|
| Darunavir: a second-generation protease inhibitor. | 2007-08-01 |
|
| Darunavir (TMC114): a new HIV-1 protease inhibitor. | 2007-08 |
|
| Development of therapeutics for AIDS: structure-based molecular targeting. | 2007-08 |
|
| Analysis of treatment costs for HIV RNA reductions and CD4 increases for darunavir versus other antiretrovirals in treatment-experienced, HIV-infected patients. | 2007-07-11 |
|
| Pharmacokinetics and antiretroviral response to darunavir/ritonavir and etravirine combination in patients with high-level viral resistance. | 2007-07-11 |
|
| 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. | 2007-07-07 |
|
| Efficacy and safety of TMC125 (etravirine) in treatment-experienced HIV-1-infected patients in DUET-1: 24-week results from a randomised, double-blind, placebo-controlled trial. | 2007-07-07 |
|
| No patient left behind--better treatments for resistant HIV infection. | 2007-07-07 |
|
| A novel bis-tetrahydrofuranylurethane-containing nonpeptidic protease inhibitor (PI), GRL-98065, is potent against multiple-PI-resistant human immunodeficiency virus in vitro. | 2007-06 |
|
| Key amprenavir resistance mutations counteract dramatic efficacy of darunavir in highly experienced patients. | 2007-05-31 |
|
| Tibotec and Aspen collaborate on Prezista. | 2007-05 |
|
| HIV-1 subtype B protease and reverse transcriptase amino acid covariation. | 2007-05 |
|
| Relative antiviral efficacy of ritonavir-boosted darunavir and ritonavir-boosted tipranavir vs. control protease inhibitor in the POWER and RESIST trials. | 2007-05 |
|
| Prediction of clinical benefits of ritonavir-boosted TMC114 from treatment effects on CD4 counts and HIV RNA. | 2007-05 |
|
| Efficacy and safety of darunavir-ritonavir at week 48 in treatment-experienced patients with HIV-1 infection in POWER 1 and 2: a pooled subgroup analysis of data from two randomised trials. | 2007-04-07 |
|
| Darunavir: promising initial results. | 2007-04-07 |
|
| When and how to use tipranavir and darunavir. | 2007-04 |
|
| The effect of different meal types on the pharmacokinetics of darunavir (TMC114)/ritonavir in HIV-negative healthy volunteers. | 2007-04 |
|
| Consensus recommendation from a group of German experts for the use of enfuvirtide in heavily pretreated HIV patients. | 2007-03-26 |
|
| New HIV treatment. | 2007-03-01 |
|
| Prezista gets EU approval. | 2007-03 |
|
| Editorial comment: impact of darunavir for salvage therapy. | 2007-03 |
|
| Darunavir: an overview of an HIV protease inhibitor developed to overcome drug resistance. | 2007-03 |
|
| Efficacy and safety of TMC114/ritonavir in treatment-experienced HIV patients: 24-week results of POWER 1. | 2007-02-19 |
|
| Darunavir (TMC114) approved by the FDA. | 2007-02 |
|
| 48-week study results show DRV's staying power. | 2007-01 |
|
| Anti-HIV agents. Darunavir and some antidepressants. | 2007-01 |
|
| 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 |
|
| Anti-HIV drugs. | 2007 |
|
| AIDS in the Third World: how to stop the HIV infection? | 2007 |
|
| Key reports from the XV International HIV Drug Resistance Workshop 2006. | 2007 |
|
| Darunavir offers potent new combo when used with enfuvirtide in ritonavir-boosted regimen. | 2007 |
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)
Created by
admin on Mon Mar 31 18:08:25 GMT 2025 , Edited by admin on Mon Mar 31 18:08:25 GMT 2025
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23725083
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m4099
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644682
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33O78XF0BW
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33O78XF0BW
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DBSALT001338
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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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