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

Study ObjectiveBecause we previously observed a significant 41% reduction in gemfibrozil exposure after 2weeks 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. DesignOpen-label, single-sequence pharmacokinetic study. SettingClinical Research Center at the National Institutes of Health. SubjectsThirteen healthy adult volunteers. InterventionSubjects received a single oral dose of fenofibrate 145mg during three study phases: before ritonavir administration, after 2weeks of administration of ritonavir 100mg twice/day, and after 2weeks of administration of lopinavir 400mg-ritonavir 100mg twice/day. Measurements and Main ResultsSerial blood samples were collected over 120hours 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 14days of ritonavir alone compared with baseline (p>0.05) and 0.87 (0.69-1.05) after 14days 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. ConclusionIn 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.