title: Lack of an Effect of Ritonavir Alone and Lopinavir-Ritonavir on the Pharmacokinetics of Fenofibric Acid in Healthy Volunteers.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  Open-label, single-sequence pharmacokinetic study.
  
  
  METHODS
  Clinical Research Center at the National Institutes of Health.
  
  
  METHODS
  Thirteen healthy adult volunteers.
  
  
  METHODS
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Pharmacy Department, NIH Clinical Center, National Institutes of Health, Bethesda, Maryland.
authors.forename: Lori A
authors.initials: LA
authors.lastname: Gordon
authors.affiliation: Pharmacy Department, NIH Clinical Center, National Institutes of Health, Bethesda, Maryland.
authors.forename: Christine Y
authors.initials: CY
authors.lastname: Malati
authors.affiliation: Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland.
authors.forename: Colleen
authors.initials: C
authors.lastname: Hadigan
authors.affiliation: Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland.
authors.forename: Mary
authors.initials: M
authors.lastname: McLaughlin
authors.affiliation: Pharmacy Department, NIH Clinical Center, National Institutes of Health, Bethesda, Maryland.
authors.forename: Raul M
authors.initials: RM
authors.lastname: Alfaro
authors.affiliation: Pharmacy Department, NIH Clinical Center, National Institutes of Health, Bethesda, Maryland.
authors.forename: Mónica M
authors.initials: MM
authors.lastname: Calderón
authors.affiliation: Critical Care Medicine Department, NIH Clinical Center, National Institutes of Health, Bethesda, Maryland.
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Kovacs
authors.affiliation: Pharmacy Department, NIH Clinical Center, National Institutes of Health, Bethesda, Maryland.
authors.forename: Scott R
authors.initials: SR
authors.lastname: Penzak
mesh_terms: D000328:Adult; D004334:Drug Administration Schedule; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D005260:Female; D011345:Fenofibrate / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D006801:Humans; D000960:Hypolipidemic Agents / Q000097:blood / Q000493:pharmacokinetics*; D061466:Lopinavir / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D019438:Ritonavir / Q000008:administration & dosage / Q000494:pharmacology*; D055815:Young Adult
chemical_list: D000960:Hypolipidemic Agents; D061466:Lopinavir; C006012:fenofibric acid; D019438:Ritonavir; D011345:Fenofibrate
keywords: fenofibrate; human immunodeficiency virus; hypertriglyceridemia; lopinavir-ritonavir; pharmacokinetics; protease inhibitor