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Ritonavir (Norvir)
 
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Last Update:  November 19, 2011
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General Reports
 
 
Ritonavir stimulates foam cell formation by activating PKC.
Xiang J, Sun G, Mu Y, et al
Chem Biol Interact. 2011 Oct 12.
Abstract

Synthesis and antimycobacterial activity of novel amino alcohols containing central core of the
anti-HIV drugs Lopinavir and Ritonavir.
 Gomes CR, Moreth M, Cardinot D,  et al
Chem Biol Drug Des. 2011 Sep 20.
Abstract

Ritonavir inhibits the two main prasugrel bioactivation pathways in vitro:
a potential drug-drug interaction in HIV patients.
 Daali Y, Ancrenaz V, Bosilkovska M, et al |
Metabolism. 2011 May 5.
Abstract

Heat-stable ritonavir tablets: a new formulation of a pharmacokinetic enhancer for HIV.
 Sherman EM, Steinberg JG.
Expert Opin Pharmacother. 2010 Dec 10.
Abstract

Efficacy of Tat-conjugated ritonavir-loaded nanoparticles in reducing HIV-1 replication in
monocyte-derived macrophages and cytocompatibility with macrophages and human neurons.
 Borgmann K, Rao KS, Labhasetwar V, Ghorpade A.
AIDS Res Hum Retroviruses. 2010 Dec 23
 Abstract

Micellar electrokinetic chromatography method development for determination of
impurities in Ritonavir.
 Carvalho AZ, El-Attug MN, Zayed SE, et al  
J Pharm Biomed Anal. 2010 Aug 16.
Abstract

Postprandial lipid effects of low-dose ritonavir vs. raltegravir in HIV-uninfected adults.
Samaras K, Richardson R, Carr A.  
AIDS. 2010 Jul 17;24(11):1727-31
 Abstract

Investigation of low-dose ritonavir on human peripheral blood mononuclear cells using
gene expression whole genome microarrays.
 Yilmaz S, Boffito M, Collot-Teixeira S, et al
Genomics. 2010 Jul;96(1):57-65.
Abstract

Boosting Dose Ritonavir Does Not Alter Peripheral Insulin Sensitivity in Healthy
HIV-Seronegative Volunteers.
 Taylor SA, Lee GA, Pao VY, et al
J Acquir Immune Defic Syndr. 2010 Jun 30.
Abstract

Protease inhibitors atazanavir, lopinavir and ritonavir are potent blockers, but
poor substrates, of ABC transporters in a broad panel of ABC transporter-
overexpressing cell lines.
Bierman WF, Scheffer GL, Schoonderwoerd A,  et al
J Antimicrob Chemother. 2010 Jun 15
 Abstract

Effect of ritonavir and atazanavir on human subcutaneous preadipocyte proliferation
and differentiation.
 Caso G, Mileva I, McNurlan MA, et al
Antiviral Res. 2010 Feb 10
 Abstract

A WEEK-IN REVIEW FEATURED REPORT
The impact of SLCO1B1 polymorphisms on the plasma concentration of lopinavir and ritonavir
in HIV-infected men.
Kohlrausch FB, de Cássia Estrela R,
Br J Clin Pharmacol. 2010 Jan;69(1):95-8.
 Abstract

A WEEK-IN-REVIEW FEATURED REPORT
How much ritonavir is needed to boost protease inhibitors? Systematic review of 17
dose-ranging pharmacokinetic trials.
 Hill A, van der Lugt J, Sawyer W, Boffito M.
AIDS. 2009 Oct 3.
 Abstract

Mutation T74S in HIV-1 subtype B and C proteases resensitizes them to ritonavir and
indinavir and confers fitness advantage.
 Soares EA, Santos AF, Gonzalez LM, et al
J Antimicrob Chemother. 2009 Aug 26.
 Abstract

A WEEK-IN-REVIEW FEATURED REPORT
 HIV monotherapy with ritonavir-boosted protease inhibitors: a systematic review.
 Bierman WF, van Agtmael MA, Nijhuis M, et al
 AIDS. 2008 Dec 24.
Abstract
 
WNT/{beta}-Catenin Signaling Is Involved in Regulation of Osteoclast Differentiation by Human
Immunodeficiency Virus Protease Inhibitor Ritonavir. Relationship to Human Immunodeficiency
Virus-Linked Bone Mineral Loss.
 Modarresi R, Xiang Z, Yin M, Laurence J.
Am J Pathol. 2008 Dec 18
 Abstract
 
Ritonavir and disulfiram have potential to inhibit caspase-1 mediated inflammation and reduce
neurological sequelae after minor blast exposure.
 Foley K, Kast RE, Altschuler EL.
Med Hypotheses. 2008 Nov 10
 Abstract
 
Ritonavir increases CD36, ABCA1 and CYP27 expression in THP-1 macrophages.
 Pou J, Rebollo A, Roglans N, et al  
Exp Biol Med (Maywood). 2008 Oct 10.
Abstract
 
An HIV protease inhibitor, ritonavir targets the nuclear factor-kappaB and inhibits the tumor growth
and infiltration of EBV-positive lymphoblastoid B cells.
Dewan MZ, Tomita M, Katano H, et al
 Int J Cancer. 2008 Sep 15.
Abstract
 
Molecular dynamic simulations analysis of ritronavir and lopinavir as SARS-CoV 3CL(pro) inhibitors.
 Nukoolkarn V, Lee VS, Malaisree M, Aruksakulwong O, Hannongbua S.
 J Theor Biol. 2008 Jul 29.
 Abstract
 
Effect of atazanavir and ritonavir on the differentiation and adipokine secretion of human subcutaneous
and omental preadipocytes.
 Jones SP, Waitt C, Sutton R, Back DJ, Pirmohamed M.  
AIDS. 2008 Jul 11;22(11):1293-8.
 Abstract
 
FULL TEXT ARTICLE
 Rate limiting steps in hepatic drug clearance: comparison of hepatocellular uptake and
metabolism with microsomal metabolism of saquinavir, nelfinavir and ritonavir.
 Parker A, Houston JB.
Drug Metab Dispos. 2008 Apr 21
 Paper
 
Estrogen prevents cholesteryl ester accumulation in macrophages induced by the HIV protease
inhibitor ritonavir.
 Wilson ME, Sengoku T, Allred KF.
J Cell Biochem. 2007 Sep 19;
 Abstract
 
Effects of ritonavir and amprenavir on insulin sensitivity in healthy volunteers.
Lee GA, Rao M, Mulligan K, et al
AIDS. 2007 Oct;21(16):2183-2190.
 Abstract
 
Immunomodulatory effects of two HIV protease inhibitors, Saquinavir and Ritonavir, on lymphocytes
from healthy seronegative individuals.
 Delmonte OM, Bertolotto G, Ricotti E, Tovo PA.
Immunol Lett. 2007 Jul 27;
Abstract
 
Human immunodeficiency virus protease inhibitor ritonavir inhibits cholesterol efflux from human
macrophage-derived foam cells.
 Wang X, Mu H, Chai H, et al 
Am J Pathol. 2007 Jul;171(1):304-14
 Abstract
 
Ritonavir 100 mg Does Not Cause QTc Prolongation in Healthy Subjects: A Possible Role as
CYP3A Inhibitor in Thorough QTc Studies.
 Sarapa N, Nickens DJ, Raber SR, et al 
Clin Pharmacol Ther. 2007 Jun 20;
 Abstract

Effects of the ritonavir price increase on the cost of protease inhibitor regimens in United States.
Lee WC, Williams KW, Chen E, et al
Manag Care Interface. 2006 Mar;19(3):27-32
 Abstract

Effect of extended exposure to grapefruit juice on cytochrome P450 3A activity in humans:
Comparison with ritonavir.
 Culm-Merdek KE, von Moltke LL, Gan L 
Clin Pharmacol Ther. 2006 Mar;79(3):243-54.
 Abstract
 
The effect of low-dose ritonavir monotherapy on fasting serum lipid concentrations.
 Shafran SD, Mashinter LD, Roberts SE. 
HIV Med. 2005 Nov;6(6):421-5.
Abstract
 
CD36 overexpression in ritonavir-treated THP-1 cells is reversed by alpha-tocopherol.
Munteanu A, Zingg JM, Ricciarelli R, Azzi A.et al
Free Radic Biol Med. 2005 Apr 15;38(8):1047-56.
 Abstract
Animal Studies
 
 
Nordihydroguaiaretic acid (NDGA) inhibits ritonavir-induced endothelial dysfunction in porcine
pulmonary arteries.
 Lü JM, Nurko J, Jiang J,  et a
 Med Sci Monit. 2011 Oct 26;17(11):BR312-318.
 Abstract

Natural antioxidant dihydroxybenzyl alcohol blocks ritonavir-induced endothelial dysfunction in
porcine pulmonary arteries and human endothelial cells.
Weakley SM, Jiang J, Lu J, et al.
Med Sci Monit. 2011 Aug 22;17(9):BR235-241.
 Abstract

UPLC-MS/MS quantification of nanoformulated ritonavir, indinavir, atazanavir, and efavirenz in
 mouse serum and tissues.
 Huang J, Gautam N, Bathena SP  J
Chromatogr B Analyt Technol Biomed Life Sci. 2011 Jul 1
 Abstract

HIV-1 Protease Inhibitor, Ritonavir: A Potent Inhibitor of CYP3A4, Enhanced the
Anticancer Effects of Docetaxel in Androgen-Independent Prostate Cancer Cells In
vitro and In vivo.
 Ikezoe T, Hisatake Y, Takeuchi T, et al   
Cancer Res. 2004 Oct 15;64(20):7426-31
 Abstract
 
Ritonavir and dexamethasone induce expression of CYP3A and P-glycoprotein in rats.
 Perloff MD, Von Moltke LL, Greenblatt DJ .et al  
Xenobiotica. 2004 Feb;34(2):133-50.
 Abstract

Low Systemic Exposure of Oral Docetaxel in Mice  Resulting from Extensive First-Pass
Metabolism Is Boosted by Ritonavir.
Bardelmeijer HA, Ouwehand M, Buckle T, et al.
Cancer Res 2002 Nov 1;62(21):6158-6164
 Abstract

Pharmacokinetic interactions between HIV-1 protease inhibitors in rats: study on
combinations of two kinds of HIV-1 protease inhibitors
Shibata N, Matsumura Y, Okamoto H, et al.
J Pharm Pharmacol 2000 Oct;52(10):1239-46
Abstract

  
In Vitro Studies
 
 
In Vitro Interaction of the HIV Protease Inhibitor Ritonavir with Herbal Constituents:
Changes in P-gp and CYP3A4 Activity.
 Patel J, Buddha B, Dey S, et al   
Am J Ther. 2004 Jul-Aug;11(4):262-277.
Abstract
 
Ritonavir-PEG 8000 amorphous solid dispersions: In vitro and in vivo evaluations.
 Law D, Schmitt EA, Marsh KC,et al   
J Pharm Sci. 2004 Mar;93(3):563-70.
 Abstract
 
Effects of the proteasome inhibitor ritonavir on glioma growth in vitro and in vivo.
 Laurent N, de Bouard S, Guillamo JS, et al 
Mol Cancer Ther. 2004 Feb;3(2):129-36.
 Abstract 
   
  A picomolar inhibitor of resistant strains of human immunodeficiency virus protease
identified by a combinatorial approach.
Rinnova M, Hradilek M, Barinka C, et al.
Arch Biochem Biophys 2000 Oct 1;382(1):22-30
Abstract 
Diagnostics/Monitoring
 
 
Clinical evaluation of the determination of plasma concentrations of darunavir, etravirine,
raltegravir and ritonavir in dried blood spot samples.
Ter Heine R, Mulder JW, van Gorp EC, et al 
Bioanalysis. 2011 May;3(10):1093-7
 Abstract

A liquid chromatography-tandem mass spectrometry assay for quantification of nevirapine,
indinavir, atazanavir, amprenavir, saquinavir, ritonavir, lopinavir, efavirenz, tipranavir, darunavir
and maraviroc in the plasma of patients infected with HIV.
 Martin J, Deslandes G, Dailly E, et al 
J Chromatogr B Analyt Technol Biomed Life Sci. 2009 Aug 3
 Abstract

Simultaneous liquid chromatographic analysis of ritonavir, quinine and 3-hydroxyquinine
in human plasma.
 Soyinka JO, Onyeji CO, Omoruyi SI.
J Chromatogr B Analyt Technol Biomed Life Sci. 2008 Dec 25.
 Abstract 
 
Evaluation of an International Pharmacopoeia method for the analysis of ritonavir by liquid chromatography.
 Yekkala RS, Ashenafi D, Mariën I,  et al
J Pharm Biomed Anal. 2008 Aug 15.
 Abstract 

Clinical ritonavir and lopinavir hypersensitivity confirmed by a specific in vitro cellular
allergen stimulation test.
Manfredi R, Sabbatani S, Bergonzi S.
 Curr HIV Res. 2007 Jul;5(4):440-2
Abstract
Pharmacokinetics
 
 
Darunavir, Ritonavir and Etravirine Pharmacokinetics in the Cervicovaginal Fluid and Blood
Plasma of HIV-Infected Women
 Patterson K, Jennings S, Falcon R,  et al
Antimicrob Agents Chemother. 2010 Dec 20
 Abstract

Ritonavir, Saquinavir and Efavirenz, but not Nevirapine, Inhibit Bile Acid Transport in Human
and Rat Hepatocytes.
 McRae MP, Lowe CM, Tian X  ,et al
J Pharmacol Exp Ther. 2006 May 23;
 Abstract
 
The long-term pharmacokinetics and safety of adding low-dose ritonavir to a
nelfinavir 1250 mg twice-daily regimen in HIV-infected patient
ts.Justesen US, Hansen IM, Andersen AB, et al
HIV Med. 2005 Sep;6(5):334-40
 Abstract
 
HIV protease inhibitor ritonavir increases endothelial monolayer permeability.
 Chen C, Lu XH, Yan S,et al
Biochem Biophys Res Commun. 2005 Aug 13;335(3):874-882
Abstract

Development and validation of a population pharmacokinetic model for ritonavir used
as a booster or as an antiviral agent in HIV-1-infected patients.
 Kappelhoff BS, Huitema AD, Crommentuyn KM, et al 
Br J Clin Pharmacol. 2005 Feb;59(2):174-82
 Abstract
Combination Therapies: General Data
 
 
Predictive Value of Pharmacokinetic-adjusted Phenotypic Susceptibility on Response to Ritonavir-enhanced
Protease Inhibitors (PI) in IN HIV-infected Patients Failing prior HIV therapy.
 Eron JJ Jr, Park JG, Haubrich R, et al 
Antimicrob Agents Chemother. 2009 Mar 23
 Abstract
 
A WEEK IN REVIEW FEATURED REPORT
 Ritonavir-Boosted Protease Inhibitor Monotherapy for the Treatment of HIV-1 Infection.
 Sahali S, Chaix ML, Delfraissy JF, Ghosn J.
AIDS Rev. 2008 Jan-Mar;10(1):4-14.
 Abstract

Performance of Six Different Ritonavir-Boosted Protease Inhibitor-Based Regimens in Heavily
Antiretroviral-Experienced HIV-Infected Patients.
 Mendoza C, Valer L, Ribera E 
HIV Clin Trials. 2006 Jul-Aug;7(4):163-71
 Abstract
 
Ritonavir Increases Plasma Amprenavir (APV) Exposure to a Similar Extent when
Coadministered with
either Fosamprenavir or APV.
 Wire MB, Baker KL, Jones LS, et al 
Antimicrob Agents Chemother. 2006 Apr;50(4):1578-80.
 Abstract
 
Ritonavir-boosted protease inhibitors, Part 1: strategies for balancing efficacy with
effects on lipids.
Cohen CJ.
 AIDS Read. 2005 Sep;15(9):462-5, 470-1, 474, 477.
 Abstract 
 
Pharmacological and therapeutic properties of ritonavir-boosted protease inhibitor
therapy in HIV-infected patients.
 Zeldin RK, Petruschke RA.  
 J Antimicrob Chemother. 2003 Dec 4
 Abstract 

A review of low-dose ritonavir in protease inhibitor combination therapy.
 Cooper CL, Van Heeswijk RP, Gallicano K, Cameron DW.
 Clin Infect Dis. 2003 Jun 15;36(12):1585-92.
 Abstract 

  
Treatment Strategies
 
 
Ritonavir greatly impairs CYP3A activity in HIV infection with chronic viral hepatitis.
 Knox TA, Oleson L, von Moltke LL, et al
J Acquir Immune Defic Syndr. 2008 Dec 1;49(4):358-68.
 Abstract
 
A WEEK IN REVIEW FEATURED REPORT
Randomized Study of Dual Versus Single Ritonavir-Enhanced Protease Inhibitors for Protease
Inhibitor-Experienced Patientswith HIV.
Collier AC, Tierney C, Downey GF, et al
HIV Clin Trials. 2008 Mar-Apr;9(2):91-102
 Abstract
 
Ritonavir and disulfiram may be synergistic in lowering active interleukin-18 levels in acute pancreatitis,
and thereby hasten recovery.
 Kast RE.  
JOP. 2008 May 8;9(3):350-3
 Abstract
 
Ritonavir-Boosted Protease Inhibitor Monotherapy for the Treatment of HIV-1 Infection.
Sahali S, Chaix ML, Delfraissy JF, Ghosn J.
AIDS Rev. 2008 Jan-Mar;10(1):4-14.
 Abstract
 
Simplifying the treatment of HIV infection with ritonavir-boosted protease inhibitors in antiretroviral-
experienced patients.
Scott JD. 
Am J Health Syst Pharm. 2005 Apr 15;62(8):809-15
 Abstract
 
The efficacy of ritonavir in the prevention of AIDS-related Kaposi's sarcoma.
 Stebbing J, Portsmouth S, Nelson M, et al 
Int J Cancer. 2004 Feb 10;108(4):631-3.
Abstract 

The role of pharmacological enhancement in protease inhibitor-based highly active
antiretroviral therapy.
 Becker SL  
 Expert Opin Investig Drugs 2003 Mar;12(3):401-12
 Abstract 

  
Non-HIV Indications
 
 
The Human Immunodeficiency Virus Protease Inhibitor Ritonavir Inhibits Lung Cancer Cells, in Part,
by Inhibition of Survivin.
Srirangam A, Milani M, Mitra R,  et al
J Thorac Oncol. 2011 Jan 25.
 Abstract 

Combination of Suberoylanilide Hydroxamic Acid and Ritonavir is Effective Against
Renal Cancer Cells.
 Sato A, Asano T, Horiguchi A, et al
Urology. 2010 Jul 12.
Abstract 

FULL-TEXT PDF ARTICLE
 Ritonavir blocks AKT signaling, activates apoptosis and inhibits migration and invasion
in ovarian cancer cells.
 Kumar S, Bryant CS, Chamala S,  et al 
Mol Cancer. 2009 Apr 22;8(1):26.
 Paper|
 
An HIV protease inhibitor, ritonavir targets the nuclear factor-kappaB and inhibits the tumor growth
and infiltration of EBV-positive lymphoblastoid B cells.
Dewan MZ, Tomita M, Katano H, et al
 Int J Cancer. 2008 Sep 15.
Abstract 

Effects of HIV Protease Inhibitor Ritonavir on Akt-Regulated Cell Proliferation in Breast
Cancer.
 Srirangam A, Mitra R, Wang M, et al
Clin Cancer Res. 2006 Mar 15;12(6):1883-1896
 Abstract 
 
The HIV protease inhibitor ritonavir synergizes with butyrate for induction of
apoptotic cell death and mediates expression of heme oxygenase-1 in DLD-1
colon carcinoma cells.
 Muhl H, Paulukat J, Hofler S, et al    
Br J Pharmacol. 2004 Oct 25
 Abstract 
 
Effects of the proteasome inhibitor ritonavir on glioma growth in vitro and in vivo.
 Laurent N, de Bouard S, Guillamo JS, et al  
Mol Cancer Ther. 2004 Feb;3(2):129-36.
 Abstract 

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