Ritonavir

Publication Title: 
The American Journal of Tropical Medicine and Hygiene

A multiple dose, parallel group study was conducted to assess for a drug-drug interaction between the pyronaridine/artesunate (PA) combination antimalarial and ritonavir. Thirty-four healthy adults were randomized (1:1) to receive PA for 3 days or PA with ritonavir (100 mg twice daily for 17 days, PA administered on Days 8-10). Pharmacokinetic parameters for pyronaridine, artesunate, and its active metabolite dihydroartemisinin (DHA) were obtained after the last PA dose and for ritonavir on Days 1 and 10.

Author(s): 
Morris, Carrie A.
Lopez-Lazaro, Luis
Jung, Donald
Methaneethorn, Janthima
Duparc, Stephan
Borghini-Fuhrer, Isabelle
Pokorny, Rolf
Shin, Chang-Sik
Fleckenstein, Lawrence
Publication Title: 
The New England Journal of Medicine

BACKGROUND: Human immunodeficiency virus (HIV) protease inhibitors show activity against Plasmodium falciparum in vitro. We hypothesized that the incidence of malaria in HIV-infected children would be lower among children receiving lopinavir-ritonavir-based antiretroviral therapy (ART) than among those receiving nonnucleoside reverse-transcriptase inhibitor (NNRTI)-based ART.

Author(s): 
Achan, Jane
Kakuru, Abel
Ikilezi, Gloria
Ruel, Theodore
Clark, Tamara D.
Nsanzabana, Christian
Charlebois, Edwin
Aweeka, Francesca
Dorsey, Grant
Rosenthal, Philip J.
Havlir, Diane
Kamya, Moses R.
Publication Title: 
Oncotarget

CUSP9 treatment protocol for recurrent glioblastoma was published one year ago. We now present a slight modification, designated CUSP9*. CUSP9* drugs--aprepitant, artesunate, auranofin, captopril, celecoxib, disulfiram, itraconazole, sertraline, ritonavir, are all widely approved by regulatory authorities, marketed for non-cancer indications. Each drug inhibits one or more important growth-enhancing pathways used by glioblastoma. By blocking survival paths, the aim is to render temozolomide, the current standard cytotoxic drug used in primary glioblastoma treatment, more effective.

Author(s): 
Kast, Richard E.
Karpel-Massler, Georg
Halatsch, Marc-Eric
Publication Title: 
The American Journal of Pathology

Clinical use of human immunodeficiency virus protease inhibitors such as ritonavir may be associated with cardiovascular disease. The objective of this study was to determine the effects and molecular mechanisms of ritonavir on cholesterol efflux from human macrophage-derived foam cells, which is a critical factor of atherogenesis. Human THP-1 monocytes and peripheral blood mononuclear cells were preincubated with acetylated low-density lipoprotein and [(3)H]cholesterol to form foam cells, which were then treated with apolipoprotein A-I for cholesterol efflux assay.

Author(s): 
Wang, Xinwen
Mu, Hong
Chai, Hong
Liao, Dan
Yao, Qizhi
Chen, Changyi
Publication Title: 
The Journal of Pharmacy and Pharmacology

Ritonavir, a protease inhibitor drug, is commonly used in AIDS therapy. As with other chemotherapeutic drugs that cause gastrointestinal adverse effects, ritonavir treatment is associated with significant nausea and vomiting. This study investigated whether Scutellaria baicalensis, and its active flavonoid constituent, baicalein, attenuate the gastrointestinal effects of ritonavir. The effects of herb administration were evaluated in ritonavir-treated rats using a rat pica model, which simulates nausea and vomiting in humans.

Author(s): 
Mehendale, Sangeeta
Aung, Han
Wang, Chong-Zhi
Tong, Robin
Foo, Adela
Xie, Jing-Tian
Yuan, Chun-Su
Publication Title: 
Clinical Cancer Research: An Official Journal of the American Association for Cancer Research

PURPOSE: To evaluate the effects of ritonavir, a potent inhibitor of CYP3A4, on the steady-state pharmacokinetics of imatinib. EXPERIMENTAL DESIGN: Imatinib pharmacokinetics were evaluated in cancer patients receiving the drug for at least 2 months, after which ritonavir (600 mg) was administered daily for 3 days. Samples were obtained on the day before ritonavir (day 1) and on the third day (day 4).

Author(s): 
van Erp, Nielka P.
Gelderblom, Hans
Karlsson, Mats O.
Li, Jing
Zhao, Ming
Ouwerkerk, Jan
Nortier, Johan W.
Guchelaar, Henk-Jan
Baker, Sharyn D.
Sparreboom, Alex
Publication Title: 
The American Journal of Pathology

The objective of this study was to determine the effects of highly active antiretroviral therapy (HAART) drugs on pulmonary endothelial function. Porcine pulmonary arteries or human pulmonary arterial endothelial cells (HPAECs) were incubated with eight HAART drugs [ritonavir, indinavir, lopinavir, zidovudine (AZT), abacavir, stavudine, didanosine (ddI), and lamivudine] individually or in combination [three HAART drugs (3-plex; indinavir, stavudine, and ddI)] at their clinical plasma concentrations for 24 hours.

Author(s): 
Wang, Xinwen
Chai, Hong
Lin, Peter H.
Yao, Qizhi
Chen, Changyi
Publication Title: 
Biochimica Et Biophysica Acta

Infection with human immunodeficiency virus (HIV) and treatment with HIV-protease inhibitor (PI)-based highly active antiretroviral therapies (HAART) is associated with dysregulated fatty acid and lipid metabolism. Enhanced lipolysis, increased circulating fatty acid levels, and hepatic and intramuscular lipid accumulation appear to contribute to insulin resistance in HIV-infected people treated with PI-based HAART. However, it is unclear whether currently prescribed HIV-PIs directly alter skeletal muscle fatty acid transport, oxidation, and storage.

Author(s): 
Richmond, Scott R.
Carper, Michael J.
Lei, Xiaoyong
Zhang, Sheng
Yarasheski, Kevin E.
Ramanadham, Sasanka
Publication Title: 
PloS One

BACKGROUND: HIV protease inhibitor (PI)-induced inflammatory response plays an important role in HIV PI-associated dyslipidemia and cardiovascular complications. This study examined the effect of berberine, a traditional herb medicine, on HIV PI-induced inflammatory response and further investigated the underlying cellular/molecular mechanisms in macrophages. METHODOLOGY AND PRINCIPAL FINDINGS: Cultured mouse J774A.1 macrophages and primary mouse macrophages were used in this study. The expression of TNF-alpha and IL-6 were detected by real-time RT-PCR and ELISA.

Author(s): 
Zha, Weibin
Liang, Guang
Xiao, Jian
Studer, Elaine J.
Hylemon, Phillip B.
Pandak, William M.
Wang, Guangji
Li, Xiaokun
Zhou, Huiping
Publication Title: 
Molecular Pharmaceutics

The development of HIV protease inhibitors (PIs) has been one of the most significant advances of the past decade in controlling HIV infection. Unfortunately, the benefits of HIV PIs are compromised by serious side effects. One of the most frequent and deleterious side effects of HIV PIs is severe gastrointestinal (GI) disorders including mucosal erosions, epithelial barrier dysfunction, and leak-flux diarrhea, which occurs in 16-62% of patients on HIV PIs.

Author(s): 
Lei, Bokai
Zha, Weibin
Wang, Yun
Wen, Cong
Studer, Elaine J.
Wang, Xuan
Jin, Fang
Wang, Guangji
Zhang, Luyong
Zhou, Huiping

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