The Influence of Ritonavir, Alone and in Combination With Lopinavir, on Fenofibric Acid Pharmacokinetics in Healthy Volunteers

2014-08-27 03:12:44 | BioPortfolio



- Patients infected with the human immunodeficiency virus (HIV) are often treated with protease inhibitors that help fight HIV infection. However, these medications often increase blood cholesterol levels, particularly triglycerides and low-density lipoproteins, and can lead to heart disease and other problems. Patients may take drugs known as fibrates (such as gemfibrozil (Lopid(Registered Trademark))) to lower triglyceride levels, but even with maximum approved doses patients often cannot reach goal triglyceride levels. Research suggests that fibrates and certain HIV medications, such as ritonavir and lopinavir/ritonavir, may interact and decrease the effectiveness of the fibrate treatment. More research is needed to determine the best drug to lower triglyceride levels in HIV patients who are receiving protease inhibitor therapy.


- To evaluate the drug-drug interaction between fenofibrate and protease inhibitors lopinavir/ritonavir and ritonavir.


- Healthy individuals between 18 and 60 years of age.


- This study will require a screening visit and 18 study visits. The screening visit will take 3 to 4 hours, and can occur 7 to 30 days before starting the study. The rest of the study, not including the screening visit, is 48 days. Three of the visits will take about 12 hours, and the remaining 15 visits will take about 1 hour.

- For study days 1 to 7, participants will take fenofibrate alone. Participants will keep a daily record of medication doses and any side effects.

- For study days 8 to 27, participants will take fenofibrate and ritonavir. Participants will keep a daily record of medication doses and any side effects.

- For study days 29 to 48, participants will take fenofibrate and lopinavir/ritonavir. Participants will keep a daily record of medication doses and any side effects.

- Participants will have regular study visits to provide blood samples for research and monitoring.


Highly active antiretroviral therapy (HAART) has enhanced the life expectancy of human immunodeficiency virus (HIV) infected patients, making HIV a manageable chronic disease for many patients. Patients with HIV are prone to lipid abnormalities secondary to HIV infection and antiretroviral therapy, particularly HIV protease inhibitors (PI). PI containing regimens that contain boosting doses of ritonavir (RTV) (i.e., 100-200 mg once or twice daily) often cause significant increases in total cholesterol, low density lipoprotein cholesterol, and triglycerides. Therapy for isolated hypertriglyceridemia includes fibric acid derivatives, such as gemfibrozil (GFZ) or fenofibrate; however, despite treatment with these agents, triglyceride levels often remain elevated in HIV infected patients treated with HAART. Many factors likely contribute to the incomplete effectiveness of fibrates in these patients. One possible contributing factor may be a clinically significant interaction between HAART and fibrates. We recently reported a mean 41 percent decrease in GFZ area under the curve when administered with the PI combination lopinavir/ritonavir (LPV/r). To determine whether a similar interaction exists with fenofibrate, this study will characterize the impact of RTV and LPV/r on the pharmacokinetic (PK) profile of fenofibrate (Tricor(Registered Trademark) formulation), after a single 145 mg oral dose, administered to healthy volunteers. In a single sequence study design, 13 subjects will receive a single 145 mg dose of fenofibrate on three occasions: before and after 14 days of RTV 100 mg twice daily, and after 14 days of LPV/r 400/100 mg twice daily. With the exclusion of the screening period, the total duration of the study will be 48 days. Fenofibric acid (FFA) PK will be determined for all 3 sampling periods and compared. Results from this study will inform us about a potentially clinically relevant drug-drug interaction between fenofibrate and RTV-boosted PI combinations. This information may therefore assist clinicians in choosing triglyceride-lowering therapy for their HIV infected patients.

Study Design

Allocation: Non-Randomized, Control: Active Control, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Crossover Assignment, Masking: Open Label




Fenofibrate, Ritonavir, Lopinavir/Ritonavir


National Institutes of Health Clinical Center, 9000 Rockville Pike
United States




National Institutes of Health Clinical Center (CC)

Results (where available)

View Results


Published on BioPortfolio: 2014-08-27T03:12:44-0400

Clinical Trials [557 Associated Clinical Trials listed on BioPortfolio]

Pharmacokinetics of Lopinavir/Ritonavir at Three Different Doses.

The successful treatment of HIV infection relies on the use of combinations of antiretroviral therapy (cART) to achieve durable viral suppression and to minimize the emergence of resistant...

GSK1349572 Drug Interaction With Etravirine and Either Darunavir/Ritonavir or Lopinavir/Ritonavir

A Phase I, open label, randomized, three period, one-way, two cohort, adaptive crossover study to evaluate the effect of darunavir/ritonavir plus etravirine and lopinavir/ritonavir plus et...

Study Comparing Lopinavir/Ritonavir (LPV/r) + Emtricitabine/Tenofovir Disoproxil Fumarate (FTC/TDF) With a Nucleoside Sparing Regimen Consisting of Lopinavir/Ritonavir + Raltegravir (RAL)

The purpose of this study is to compare the safety, tolerability and antiviral activity of the lopinavir/ritonavir tablet when administered in combination with reverse transcriptase inhibi...

Study of Lopinavir, Ritonavir, Tenofovir and Emtricitabine in HIV-Infected Antiretroviral Naïve Subjects

The purpose of this study is to compare the safety, tolerability and antiviral activity between once-daily (QD) and twice-daily (BID) dosing of lopinavir/ritonavir and to further character...

Comparison of Two Dosing Regimens of GW433908/Ritonavir Versus Lopinavir/Ritonavir for 48 Weeks in HIV Patients Who Have Taken Protease Inhibitors and Experienced Virological Failure

The purpose of this study is to test 2 different dosing regimens of GW433908/ritonavir (RTV) versus lopinavir (LPV)/RTV when each is given with 2 active reverse transcriptase inhibitors (...

PubMed Articles [76 Associated PubMed Articles listed on BioPortfolio]

Metabolic effects of initiating lopinavir/ritonavir-based regimens among young children: 7-year follow-up of the IMPAACT P1060 trial.

To estimate the long-term metabolic effects of initiating a lopinavir/ritonavir (LPV/r)-based regimen as first-line therapy for HIV-infected children less than three years of age in resource-limited s...

An Innovative, Collaborative, and Strategic Approach to Proactively Evaluate and Update Drug Interactions Based on Prescribing Information of Newly Approved Medicinal Products.

Drug-drug interaction (DDIs) are evaluated using pharmacokinetic (PK) simulation models, clinical studies, and scientific publications throughout drug development. DDIs with Norvir (ritonavir) and com...

Evaluation of adhesion molecules and immune parameters in HIV-infected patients treated with an atazanavir/ritonavir- compared with a lopinavir/ritonavir-based regimen.

To evaluate changes in pro-atherosclerotic biomarkers and endothelial function in patients initiating two different PI-based regimens as part of ART.

Birth Outcomes for Pregnant Women with HIV Using Tenofovir-Emtricitabine.

In a previous trial of antiretroviral therapy (ART) involving pregnant women with human immunodeficiency virus (HIV) infection, those randomly assigned to receive tenofovir, emtricitabine, and ritonav...

Simultaneous quantitation of zidovudine, efavirenz, lopinavir and ritonavir in human hair by liquid chromatography-atmospheric pressure chemical ionization-tandem mass spectrometry.

Nowadays, zidovudine, efavirenz, lopinavir and ritonavir are important components of the second-line antiretroviral therapeutic regimen of National Free Antiretroviral Treatment Program in China. The ...

Medical and Biotech [MESH] Definitions

An HIV protease inhibitor used in a fixed-dose combination with RITONAVIR. It is also an inhibitor of CYTOCHROME P-450 CYP3A.

An HIV protease inhibitor that works by interfering with the reproductive cycle of HIV.

An antilipemic agent which reduces both CHOLESTEROL and TRIGLYCERIDES in the blood.

More From BioPortfolio on "The Influence of Ritonavir, Alone and in Combination With Lopinavir, on Fenofibric Acid Pharmacokinetics in Healthy Volunteers"

Quick Search


Relevant Topics

Human Immuno Deficiency Virus (HIV)
Human Immunodeficiency Virus (HIV), the causative agent of AIDS. The Human Immunodeficiency Virus, more commonly known as HIV, is a member of the lentivirus sub-set of the retrovirus family of pathogens. It causes AIDS, or Acquired Immuno Deficiency Sy...

AIDS; Acquired Immune Deficiency Syndrome. HIV; Human Immunodeficiency Virus HIV infection causes AIDS. HIV infection also causes the production of anti-HIV antibodies, which forms the test for HIV in patients. People who have the HIV antibodies are ...

Searches Linking to this Trial