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

• Published in: Pharmacotherapy Vol. 36; no. 1; p. 49
• Main Authors: Gordon, Lori A, Malati, Christine Y, Hadigan, Colleen, McLaughlin, Mary, Alfaro, Raul M, Calderón, Mónica M, Kovacs, Joseph A, Penzak, Scott R
• Format: Journal Article
• Language: English
• Published: United States 01.01.2016
• Subjects: Adult; Drug Administration Schedule; Drug Interactions; Drug Therapy, Combination; Female; Fenofibrate - analogs & derivatives; Fenofibrate - blood; Fenofibrate - pharmacokinetics; Humans; Hypolipidemic Agents - blood; Hypolipidemic Agents - pharmacokinetics; Lopinavir - administration & dosage; Lopinavir - pharmacology; Male; Middle Aged; Ritonavir - administration & dosage; Ritonavir - pharmacology; Young Adult; human immunodeficiency virus; hypertriglyceridemia; pharmacokinetics; protease inhibitor; fenofibrate; lopinavir-ritonavir
• ISSN: 1875-9114
• DOI: 10.1002/phar.1682

Because 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. Open-label, single-sequence pharmacokinetic study. Clinical Research Center at the National Institutes of Health. Thirteen healthy adult volunteers. 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/day, and after 2 weeks of administration of lopinavir 400 mg-ritonavir 100 mg twice/day. 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. 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.