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DRUG:

ritonavir

i
Other names: A 84538, ABT 538
Associations
Company:
Generic mfg.
Drug class:
Protease inhibitor
Associations
18d
PROLIFIC: ImPROving Quality of LIFe in the Long COVID Patient (clinicaltrials.gov)
P2, N=219, Completed, Karolinska Institutet | Active, not recruiting --> Completed
Trial completion • HEOR
|
ritonavir
20d
New P1 trial • Metastases
|
trastuzumab rezetecan (SHR-A1811) • itraconazole • ritonavir
25d
STARLITE for Unresectable High-Grade Gliomas (clinicaltrials.gov)
P1, N=24, Not yet recruiting, University of Miami | Trial completion date: May 2029 --> Mar 2030 | Initiation date: Nov 2024 --> Mar 2025 | Trial primary completion date: May 2028 --> Mar 2029
Trial completion date • Trial initiation date • Trial primary completion date
|
temozolomide • ritonavir
3ms
PROLIFIC: imPROving Quality of LIFe In the Long COVID Patient (clinicaltrials.gov)
P2, N=180, Active, not recruiting, Karolinska Institutet | Recruiting --> Active, not recruiting | N=400 --> 180 | Trial completion date: Mar 2024 --> Nov 2024 | Trial primary completion date: Jan 2024 --> Nov 2024
Enrollment closed • Enrollment change • Trial completion date • Trial primary completion date • HEOR
|
ritonavir
3ms
A Study of Extending Relugolix Dosing Intervals Through Addition of Itraconazole or Ritonavir in Prostate Cancer Patients (clinicaltrials.gov)
P1, N=60, Terminated, University of Chicago | N=100 --> 60 | Trial completion date: Apr 2025 --> Aug 2024 | Recruiting --> Terminated | Trial primary completion date: Apr 2025 --> Aug 2024; Terminated by the PI
Enrollment change • Trial completion date • Trial termination • Trial primary completion date
|
itraconazole • Orgovyx (relugolix) • ritonavir
3ms
Enrollment open
|
Tybost (cobicistat) • Genvoya (elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide) • ritonavir
5ms
A Phase 1/2a Study of DB-1303/BNT323 in Advanced/Metastatic Solid Tumors (clinicaltrials.gov)
P1/2, N=766, Recruiting, DualityBio Inc. | Trial completion date: Oct 2025 --> Oct 2027 | Trial primary completion date: Jun 2025 --> Apr 2026
Trial completion date • Trial primary completion date • Metastases
|
HER-2 (Human epidermal growth factor receptor 2)
|
Perjeta (pertuzumab) • trastuzumab pamirtecan (BNT323) • itraconazole • ritonavir
5ms
Inhibition of human DNA alkylation damage repair enzyme ALKBH2 by HIV protease inhibitor ritonavir. (PubMed, DNA Repair (Amst))
Interestingly, we observed that one of the inhibitors, ritonavir, could inhibit ALKBH2-mediated DNA repair significantly via competitive inhibition and sensitized cancer cells to alkylating agent methylmethane sulfonate (MMS). This work may provide new insights into the possibilities of utilizing HIV protease inhibitor ritonavir as a DNA repair antagonist.
Journal
|
ALKBH2 (AlkB Homolog 2)
|
ritonavir
6ms
Evaluate the Safety, Tolerability, and Antiviral Activity of GLS4 With Ritonavir in Patients With Chronic HBV Infection (clinicaltrials.gov)
P2, N=250, Completed, Sunshine Lake Pharma Co., Ltd. | Recruiting --> Completed | Trial completion date: May 2023 --> Sep 2023
Trial completion • Trial completion date • Combination therapy
|
ritonavir
7ms
Oral Docetaxel (ModraDoc/r) in Combination With Hormonal Treatment and Radiation Therapy in High-risk Prostate Cancer (clinicaltrials.gov)
P1, N=24, Terminated, The Netherlands Cancer Institute | Unknown status --> Terminated; low inclusion of patients and availability of the IP
Trial termination • Combination therapy
|
docetaxel oral/ritonavir (ModraDoc006/r) • ritonavir
7ms
STARLITE for Unresectable High-Grade Gliomas (clinicaltrials.gov)
P1, N=24, Not yet recruiting, University of Miami
New P1 trial
|
temozolomide • ritonavir
7ms
Peginterferon Lambda and Lonafarnib Boosted With Ritonavir 48-Week Combination Therapy for Delta Hepatitis (clinicaltrials.gov)
P2, N=0, Withdrawn, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) | N=30 --> 0 | Trial completion date: Oct 2028 --> May 2024 | Not yet recruiting --> Withdrawn | Trial primary completion date: Oct 2027 --> May 2024
Enrollment change • Trial completion date • Trial withdrawal • Trial primary completion date • Combination therapy
|
ritonavir
8ms
Clinical assessment of momelotinib drug-drug interactions via CYP3A metabolism and transporters. (PubMed, Clin Transl Sci)
Momelotinib-approved for treatment of myelofibrosis in adults with anemia-and its major active metabolite, M21, were assessed as drug-drug interaction (DDI) victims with a strong cytochrome P450 (CYP) 3A4 inhibitor (multiple-dose ritonavir), an organic anion transporting polypeptide (OATP) 1B1/1B3 inhibitor (single-dose rifampin), and a strong CYP3A4 inducer (multiple-dose rifampin). Momelotinib DDI perpetrator potential (multiple-dose) was evaluated with CYP3A4 and breast cancer resistance protein (BCRP) substrates (midazolam and rosuvastatin, respectively)...Safety findings were mild in this short-term study in healthy volunteers. This analysis suggests that momelotinib interactions with OATP1B1/1B3 inhibitors and BCRP substrates may warrant monitoring for adverse reactions or dose adjustments.
Journal
|
CYP3A4 (Cytochrome P450, family 3, subfamily A, polypeptide 4)
|
Ojjaara (momelotinib) • midazolam hydrochloride • rifampicin • ritonavir
9ms
New P4 trial
|
Tybost (cobicistat) • Genvoya (elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide) • ritonavir
10ms
Switching From Protease Inhibitor/Ritonavir to Generic Single Tablet Regimen of Tenofovir Alafenamide/Emtricitibine/Dolutegravir (clinicaltrials.gov)
P3, N=170, Completed, The HIV Netherlands Australia Thailand Research Collaboration | Active, not recruiting --> Completed | Trial completion date: Dec 2022 --> Apr 2023 | Trial primary completion date: Dec 2022 --> Apr 2023
Trial completion • Trial completion date • Trial primary completion date
|
ritonavir
11ms
Ritonavir reverses resistance to docetaxel and cabazitaxel in prostate cancer cells with acquired resistance to docetaxel. (PubMed, Cancer Drug Resist)
Both parental and resistant cell lines were treated with the taxane drugs docetaxel and cabazitaxel in combination with the P-gp/CYP3A4 inhibitor ritonavir and the P-gp inhibitor elacridar. In a Caco-2 P-gp transporter assay, functional inhibition of P-gp-mediated transport of docetaxel with ritonavir was demonstrated. Our results demonstrate that ritonavir restores sensitivity to both docetaxel and cabazitaxel in docetaxel-resistant cell lines, most likely by inhibiting P-gp-mediated drug efflux.
Preclinical • Journal
|
ABCB1 (ATP Binding Cassette Subfamily B Member 1)
|
docetaxel • cabazitaxel • elacridar (GF120918) • ritonavir
12ms
HERV-K Suppression Using Antiretroviral Therapy in Volunteers With Amyotrophic Lateral Sclerosis (ALS) (clinicaltrials.gov)
P1, N=122, Completed, National Institute of Neurological Disorders and Stroke (NINDS) | Active, not recruiting --> Completed | Trial completion date: Oct 2024 --> May 2023 | Active, not recruiting --> Completed
Trial completion • Trial completion date
|
ritonavir
1year
A104: Study of DS-8201a for Participants With Advanced Solid Malignant Tumors (clinicaltrials.gov)
P1, N=40, Completed, Daiichi Sankyo Co., Ltd. | Active, not recruiting --> Completed | Trial completion date: Mar 2024 --> Sep 2023
Trial completion • Trial completion date
|
HER-2 (Human epidermal growth factor receptor 2)
|
HER-2 expression
|
Enhertu (fam-trastuzumab deruxtecan-nxki) • itraconazole • ritonavir
1year
Population Pharmacokinetics of trastuzumab deruxtecan (T-DXd) in HER2-positive breast cancer subjects: analyses across 12 Phase 1-3 studies (SABCS 2023)
Covariates previously detected to be statistically significant (cancer type, tumor size, albumin, race-country, body weight and sex for T-DXd; age, cancer type, AST, total bilirubin, ritonavir or itraconazole use, race-country, formulation and body weight for DXd) were retained in the PopPK model. Similar T-DXd and DXd exposures were obtained for the recommended dosing of 5.4 mg/kg Q3W T-DXd in BC subjects across categories of hepatic function, renal function, region, race-country, HER2 status, and line of therapy.
Clinical • P1 data • PK/PD data
|
HER-2 (Human epidermal growth factor receptor 2)
|
HER-2 positive • HER-2 negative
|
Enhertu (fam-trastuzumab deruxtecan-nxki) • itraconazole • ritonavir
1year
A Study of DB-1303 in Advanced/Metastatic Solid Tumors (clinicaltrials.gov)
P1/2, N=631, Recruiting, DualityBio Inc. | N=463 --> 631
Enrollment change • Metastases
|
HER-2 (Human epidermal growth factor receptor 2)
|
HER-2 positive • HER-2 expression
|
Perjeta (pertuzumab) • trastuzumab pamirtecan (BNT323) • itraconazole • ritonavir
1year
Trial completion
|
CD4 (CD4 Molecule)
|
ritonavir
over1year
A104: Study of DS-8201a for Participants With Advanced Solid Malignant Tumors (clinicaltrials.gov)
P1, N=40, Active, not recruiting, Daiichi Sankyo Co., Ltd. | Trial completion date: Sep 2023 --> Mar 2024
Trial completion date • Metastases
|
HER-2 (Human epidermal growth factor receptor 2)
|
HER-2 expression
|
Enhertu (fam-trastuzumab deruxtecan-nxki) • itraconazole • ritonavir
over1year
Screening of Phyllanthus niruri Leaves Phytoconstituents for Antiviral and Antibacterial Activity by Molecular Docking Studies. (PubMed, Adv Exp Med Biol)
For additional docking investigations with distinct proteins, the leaf chemicals are assessed, that is, the crystal structure of serine protease hepsin in complex with inhibitor [PDB ID:5 CE1] for antiviral activity human topoisomerase II beta in complex with DNA and etoposide [PDB ID:3QX3] and crystal structure of E. coli GyraseB 24 kDa in complex with 4-(4-bromo-1H-pyrazol-1-yl)-6-[(ethylcarbamoyl)amino]-N-(pyridin-3-yl) pyridine-3-carboxamide [PDB ID: 6F86] for antibacterial activity and have been selected. To evaluate the in silico results and grading of virtual screening, or molecular docking, ritonavir antiviral activity and ampicillin for antibacterial activity were used as a benchmark.
Journal
|
etoposide IV • ritonavir
over1year
Phase I trial of the multi-kinase inhibitor cabozantinib, a CYP3A4 substrate, plus CYP3A4 interacting antiretroviral therapy in people living HIV and cancer (AMC087). (PubMed, Clin Cancer Res)
Cabozantinib as a single agent should be initiated at 20 mg daily and 60 mg daily when taken concurrently with ARVs that are strong CYP3A4 inhibitors and inducers, respectively, with consideration for subsequent escalation per current cabozantinib guidelines.
P1 data • Journal
|
AXL (AXL Receptor Tyrosine Kinase) • CYP3A4 (Cytochrome P450, family 3, subfamily A, polypeptide 4)
|
Cabometyx (cabozantinib tablet) • Tybost (cobicistat) • efavirenz • ritonavir
over1year
A case of a 32-year-old Acquired Immunodeficiency Syndrome patient with Kaposi Sarcoma (WCD 2023)
Lamivudine plus Zidovudine and Lopinavir plus Ritonavir were given as antiretroviral medications. Compliance in antiretroviral therapy is significant and effective in the control of the disease. Extensive mucocutaneous involvement requires palliative and multispecialty management
Clinical
|
CD34 (CD34 molecule) • CD31 (Platelet and endothelial cell adhesion molecule 1) • PECAM1 (Platelet And Endothelial Cell Adhesion Molecule 1)
|
ritonavir
over1year
Report of consensus panel 5 from the 11th international workshop on Waldenstrom's macroglobulinemia on COVID-19 prophylaxis and management. (PubMed, Semin Hematol)
Patients under treatment with rituximab or BTK-inhibitors have lower antibody responses against SARS-CoV-2; thus, they should continue to follow preventive measures, including mask wearing and avoiding crowded places...Coadministration of ibrutinib or venetoclax with ritonavir should be avoided. In these patients, remdesivir offers an effective alternative. Patients with asymptomatic or oligosymptomatic COVID-19 should not interrupt treatment with a BTK inhibitor. Infection prophylaxis is essential in patients with WM and include general preventive measures, prophylaxis with antivirals and vaccination against common pathogens including SARS-CoV-2, influenza, and S. pneumoniae.
Journal • IO biomarker
|
Venclexta (venetoclax) • Imbruvica (ibrutinib) • Rituxan (rituximab) • ritonavir
over1year
A104: Study of DS-8201a for Participants With Advanced Solid Malignant Tumors (clinicaltrials.gov)
P1, N=40, Active, not recruiting, Daiichi Sankyo Co., Ltd. | Trial completion date: Mar 2023 --> Sep 2023
Trial completion date • Metastases
|
HER-2 (Human epidermal growth factor receptor 2)
|
HER-2 expression
|
Enhertu (fam-trastuzumab deruxtecan-nxki) • itraconazole • ritonavir
almost2years
Mouse mammary tumor virus is implicated in severity of colitis and dysbiosis in the IL-10 mouse model of inflammatory bowel disease. (PubMed, Microbiome)
This study suggests that immunogenetically manipulated mice with deletion of IL-10 may have reduced capacity to contain MMTV infection in a mouse-strain-specific manner, and the antiviral inflammatory responses may contribute to the complexity of IBD with the development of colitis and dysbiosis. Video Abstract.
Preclinical • Journal • IO biomarker
|
IFNG (Interferon, gamma) • IL10 (Interleukin 10)
|
ritonavir
2years
A frequent PLCγ1 mutation in adult T-cell leukemia/lymphoma determines functional properties of the malignant cells. (PubMed, Biochim Biophys Acta Mol Basis Dis)
Consistent with observations from clinical studies, our data provide direct evidence that activated variants of the PLCγ1 enzyme contribute to the properties of the malignant T-cell clone in ATL.
Journal
|
CCL2 (Chemokine (C-C motif) ligand 2) • CCL22 (C-C Motif Chemokine Ligand 22)
|
Imbruvica (ibrutinib) • ritonavir
over2years
AMPKα2/HNF4A/BORIS/GLUT4 pathway promotes hepatocellular carcinoma cell invasion and metastasis in low glucose microenviroment. (PubMed, Biochem Pharmacol)
We also found that HNF4A agonist (Benfluorex) and GLUT4 inhibitor (antiviral drug Ritonavir) can suppress HCC cell proliferation and glucose uptake. Taken together, these results all suggest that activation of the AMPKα2/HNF4A/BORIS/GLUT4 signaling pathway in a low-glucose microenvironment can significantly promote the invasion and metastasis of HCC cells, while HNF4A and GLUT4 may have important potential applications as prognostic or drug target molecules.
Journal
|
HNF1A (HNF1 Homeobox A) • PKM (Pyruvate Kinase M1/2)
|
ritonavir
over2years
Synergistic combination of ritonavir and cisplatin as an efficacious therapy in human cervical cancer cells: a computational drug discovery and in vitro insight. (PubMed, J Biomol Struct Dyn)
These observations suggest that anti-viral compound (RTV) could act synergistically with Cisplatin for cervical cancer therapy. However, further studies are warranted to investigate the combinatorial mode of action of RTV and Cisplatin on different molecular pathways to have a translational outcome in cervical cancer.Communicated by Ramaswamy H. Sarma.
Preclinical • Journal
|
ALK (Anaplastic lymphoma kinase)
|
cisplatin • ritonavir
over2years
Prostate Apoptosis Response-4 (Par-4): A Novel Target in Pyronaridine-Induced Apoptosis in Glioblastoma (GBM) Cells. (PubMed, Cancers (Basel))
Synergistic activity was observed when PYR was combined with Doxorubicin and Ritonavir. Thus, our study demonstrates for the first time that PYR can be repurposed against GBM with a novel mechanism of action involving Par-4. Herewith, we discuss the role of upregulated Par-4 in a highly interconnected signaling network thereby advocating its importance as a therapeutic target.
Journal
|
CDH1 (Cadherin 1) • CASP3 (Caspase 3)
|
CDH1 expression
|
doxorubicin hydrochloride • ritonavir
over2years
Simultaneous Delivery of Doxorubicin and Protease Inhibitor Derivative to Solid Tumors via Star-Shaped Polymer Nanomedicines Overcomes P-gp- and STAT3-Mediated Chemoresistance. (PubMed, Biomacromolecules)
The derivative of protease inhibitor ritonavir (5-methyl-4-oxohexanoic acid ritonavir ester; RD) was recently recognized as a potent P-gp inhibitor and cancerostatic drug inhibiting the proteasome and STAT3 signaling. Star-RD + Dox efficiently inhibited STAT3 signaling and induced caspase-3 activation and DNA fragmentation in cancer cells in vivo. Importantly, Star-RD + Dox was found to have superior antitumor activity in terms of tumor growth inhibition and increased survival of mice bearing P-gp-expressing tumors.
Journal
|
STAT3 (Signal Transducer And Activator Of Transcription 3) • CASP3 (Caspase 3)
|
doxorubicin hydrochloride • ritonavir
over2years
Long Noncoding RNAs Hepatocyte Nuclear Factor 4A Antisense RNA 1 and Hepatocyte Nuclear Factor 1A Antisense RNA 1 are Involved in Ritonavir-induced Cytotoxicity in Hepatoma Cells. (PubMed, FASEB J)
Ritonavir (RTV), a pharmacoenhancer used in anti-HIV regimens, can induce liver damage. Increased susceptibility to RTV-induced liver injury caused by the PXR activator rifampicin was attenuated by HNF4A-AS1 overexpression or HNF1A-AS1 knockdown. Taken together, these results revealed that HNF4A-AS1 and HNF1A-AS1 modulated RTV-induced hepatotoxicity by regulating CYP3A4 expression, primarily by affecting the binding of PXR and histone modification status in the CYP3A4 promoter.
Journal
|
CYP3A4 (Cytochrome P450, family 3, subfamily A, polypeptide 4) • HNF1A (HNF1 Homeobox A)
|
rifampicin • ritonavir
over2years
Interactions between HIV protease inhibitor ritonavir and human DNA repair enzyme ALKBH2: a molecular dynamics simulation study. (PubMed, Mol Divers)
Using molecular dynamics simulation, we elucidated the molecular details of Ritonavir-ALKBH2 interaction. The present work highlights that Ritonavir might be used to target the ALKBH2-mediated DNA alkylation repair.
Journal
|
ALKBH2 (AlkB Homolog 2)
|
ritonavir
over2years
Safety and Tolerability of Carboplatin and Paclitaxel in Cancer Patients with HIV (AMC-078), an AIDS Malignancy Consortium (AMC) Study. (PubMed, Oncologist)
Full doses of PCb chemotherapy are tolerable when given concurrently with ART in people living with human immunodeficiency virus with cancer, including patients receiving CYP3A4 inhibitors.
Journal
|
CD4 (CD4 Molecule)
|
carboplatin • paclitaxel • ritonavir
almost3years
A104: Study of DS-8201a for Participants With Advanced Solid Malignant Tumors (clinicaltrials.gov)
P1, N=40, Active, not recruiting, Daiichi Sankyo Co., Ltd. | Trial completion date: Mar 2022 --> Mar 2023
Trial completion date
|
HER-2 (Human epidermal growth factor receptor 2)
|
HER-2 expression
|
Enhertu (fam-trastuzumab deruxtecan-nxki) • itraconazole • ritonavir
almost3years
Human endogenous retrovirus type K promotes proliferation and confers sensitivity to anti-retroviral drugs in Merlin-negative schwannoma and meningioma. (PubMed, Cancer Res)
Furthermore, FDA-approved retroviral protease inhibitors ritonavir, atazanavir, and lopinavir reduced proliferation of schwannoma and grade I meningioma cells. Furthermore, FDA-approved retroviral protease inhibitors ritonavir, atazanavir, and lopinavir reduced proliferation of schwannoma and grade I meningioma cells. These results identify HERV-K as a critical regulator of progression in Merlin-deficient tumours and offer potential strategies for therapeutic intervention.
Journal
|
NF2 (Neurofibromin 2) • IL17RB (Interleukin 17 Receptor B)
|
ritonavir
almost3years
Long Noncoding RNAs Hepatocyte Nuclear Factor 4A Antisense RNA 1 and Hepatocyte Nuclear Factor 1A Antisense RNA 1 are Involved in Ritonavir-induced Cytotoxicity in Hepatoma Cells. (PubMed, Drug Metab Dispos)
Ritonavir (RTV), a pharmacoenhancer used in anti-HIV regimens, can induce liver damage. Significance Statement HNF4A-AS1 and HNF1A-AS1, transcribed separately from neighboring antisense genes of the human transcription factor genes HNF4A and HNF1A, were identified as lncRNAs that can affect RTV-induced hepatotoxicity and susceptibility to RTV-induced hepatotoxicity caused by rifampicin exposure, mainly by affecting the expression of CY3A4 via alterations in PXR enrichment and histone modification status in the CYP3A4 promoter. This discovery provides directions for further research on the mechanisms of RTV-induced liver injury.
Journal
|
CYP3A4 (Cytochrome P450, family 3, subfamily A, polypeptide 4) • HNF1A (HNF1 Homeobox A)
|
rifampicin • ritonavir
3years
Journal • Epigenetic controller
|
CYP3A4 (Cytochrome P450, family 3, subfamily A, polypeptide 4)
|
ritonavir
over3years
Pharmacokinetics, Safety, and Efficacy of Trastuzumab Deruxtecan With Concomitant Ritonavir or Itraconazole in Patients With HER2-Expressing Advanced Solid Tumors. (PubMed, Clin Cancer Res)
T-DXd was safely combined with ritonavir or itraconazole without clinically meaningful impact on T-DXd or DXd pharmacokinetics.
Clinical • PK/PD data • Journal
|
HER-2 (Human epidermal growth factor receptor 2)
|
HER-2 expression
|
Enhertu (fam-trastuzumab deruxtecan-nxki) • itraconazole • ritonavir