Lack of an Effect of Ritonavir Alone and Lopinavir-Ritonavir on the Pharmacokinetics of Fenofibric Acid in Healthy Volunteers

Abstract

Study Objective As we previously observed a significant 41% reduction in gemfibrozil exposure after 2 weeks of lopinavir-ritonavir administration, we sought to determine the influence of lopinavir-ritonavir and ritonavir alone on the pharmacokinetics of fenofibric acid, an alternative to gemfibrozil for the treatment of elevated triglyceride levels. Design Open-label, single-sequence pharmacokinetic study. Setting Clinical Research Center at the National Institutes of Health. Subjects Thirteen healthy adult volunteers. Intervention Subjects received a single oral dose of fenofibrate 145 mg during three study phases: before ritonavir administration, after 2 weeks of administration of ritonavir 100 mg twice daily, and after 2 weeks of administration of lopinavir 400 mg–ritonavir 100 mg twice daily. Measurements and Main Results Serial blood samples were collected over 120 hours for determination of fenofibric acid concentrations. Fenofibric acid pharmacokinetic parameter values were compared before and after concomitant ritonavir or lopinavir-ritonavir administration. The geometric mean ratios (90% confidence intervals) for fenofibric acid area under the plasma concentration–time curve were 0.89 (0.77–1.01) after 14 days of ritonavir alone compared with baseline (p>0.05) and 0.87 (0.69–1.05) after 14 days of lopinavir-ritonavir compared with baseline (p>0.05). Study drugs were generally well tolerated; all adverse events were mild or moderate, transient, and resolved without intervention. Conclusion In contrast to a significant interaction between gemfibrozil and lopinavir-ritonavir, neither lopinavir-ritonavir nor ritonavir alone altered the pharmacokinetics of fenofibric acid in healthy volunteers. These data suggest that fenofibrate remains an important option in human immunodeficiency virus–infected patients receiving common ritonavir-boosted therapy.

Reverse Translational Study of Fenofibrate's Observed Effects in Diabetes‐Associated Retinopathy

“…RPECs were viable across all concentrations of fenofibrate used in the cytotoxicity experiments ( Figure ). Concentrations of fenofibrate 1–50 μM were used in the experimental treatment groups as they represent expected plasma concentrations across the clinical spectrum (i.e., the range of fenofibrate's peak plasma concentration C max in plasma is between 26 and 30 μM) …”

Lopinavir-Ritonavir in SARS-CoV-2 Infection and Drug-Drug Interactions with Cardioactive Medications

“…Compared with baseline, RTV decreased fenofibrate AUC by 11% (p > 0.05) and C max was unchanged, and L/R decreased fenofibrate AUC by 13% (p > 0.05) and C max was unchanged. The authors concluded that fenofibrate can safely be given with either L/R or ritonavir alone [42]. The same authors reported a significant 41% reduction in gemfibrozil exposure after 2 weeks of L/R administration.…”

“…Aspirin, Prasugrel [20], Cangrelor, GPIIb/IIIa Clopidogrel [16,17] Ticagrelor [24][25][26], Vorapaxar Lipids lowering agents Pitavastatin [36,37], pravastatin, Fluvastatin, Ezetimibe, Fenofibrate [42], PCSK9inhibitors…”

A Fenofibrate Diet Prevents Paclitaxel-Induced Peripheral Neuropathy in Mice

“…Fenofibric acid (90568-10MG, Sigma-Aldrich, St. Louis, MO, USA) was dissolved in DMSO and added to the incubation medium to achieve the indicated drug concentrations. The in vitro concentrations of fenofibric acid were determined from the Cmax plasma concentrations from previously reported patient samples [ 49 , 50 , 51 ]. Cells were treated for 24 h; the DMSO concentration used never exceeded 0.1% DMSO.…”