title: Influence of Panax ginseng on the steady state pharmacokinetic profile of lopinavir-ritonavir in healthy volunteers.
abstract: OBJECTIVE
  Panax ginseng has been shown in preclinical studies to modulate cytochrome P450 enzymes involved in the metabolism of HIV protease inhibitors. Therefore, the purpose of this study was to determine the influence of P. ginseng on the pharmacokinetics of the HIV protease inhibitor combination lopinavir-ritonavir (LPV-r) in healthy volunteers.
  
  
  METHODS
  Single-sequence, open-label, single-center pharmacokinetic investigation.
  
  
  METHODS
  Government health care facility.
  
  
  METHODS
  Twelve healthy human volunteers.
  
  
  RESULTS
  Twelve healthy volunteers received LPV-r (400-100 mg) twice/day for 29.5 days. On day 15 of LPV-r administration, serial blood samples were collected over 12 hours for determination of lopinavir and ritonavir concentrations. On study day 16, subjects began taking P. ginseng 500 mg twice/day, which they continued for 2 weeks in combination with LPV-r. On day 30 of LPV-r administration, serial blood samples were again collected over 12 hours for determination of lopinavir and ritonavir concentrations. Lopinavir and ritonavir pharmacokinetic parameter values were determined using noncompartmental methods, and preadministration and postadministration ginseng values were compared using a Student t test, where p<0.05 was accepted as statistically significant.
  
  
  CONCLUSIONS
  Neither lopinavir nor ritonavir steady-state pharmacokinetics were altered by 2 weeks of P. ginseng administration to healthy human volunteers. Thus, a clinically significant interaction between P. ginseng and LPV-r is unlikely to occur in HIV-infected patients who choose to take these agents concurrently. It is also unlikely that P. ginseng will interact with other ritonavir-boosted protease inhibitor combinations, although confirmatory data are necessary.
authors.affiliation: Clinical Research Center, Clinical Center Pharmacy Department, National Institutes of Health, Bethesda, Maryland.
authors.forename: Mónica M
authors.initials: MM
authors.lastname: Calderón
authors.forename: Cheryl L
authors.initials: CL
authors.lastname: Chairez
authors.forename: Lori A
authors.initials: LA
authors.lastname: Gordon
authors.forename: Raul M
authors.initials: RM
authors.lastname: Alfaro
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Kovacs
authors.forename: Scott R
authors.initials: SR
authors.lastname: Penzak
mesh_terms: D000328:Adult; D065701:Cytochrome P-450 CYP3A Inducers / Q000009:adverse effects*; D065692:Cytochrome P-450 CYP3A Inhibitors / Q000097:blood / Q000493:pharmacokinetics*; D019587:Dietary Supplements / Q000009:adverse effects*; D004338:Drug Combinations; D005260:Female; D018565:Food-Drug Interactions; D017320:HIV Protease Inhibitors / Q000097:blood / Q000493:pharmacokinetics*; D006207:Half-Life; D006801:Humans; D007155:Immunologic Factors / Q000009:adverse effects; D061466:Lopinavir / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D008396:Maryland; D008657:Metabolic Clearance Rate; D054579:National Institute of Allergy and Infectious Diseases (U.S.); D018697:Nootropic Agents / Q000009:adverse effects; D005894:Panax / Q000009:adverse effects*; D018517:Plant Roots / Q000009:adverse effects; D019438:Ritonavir / Q000097:blood / Q000493:pharmacokinetics*; D014481:United States; D055815:Young Adult
chemical_list: D065701:Cytochrome P-450 CYP3A Inducers; D065692:Cytochrome P-450 CYP3A Inhibitors; D004338:Drug Combinations; D017320:HIV Protease Inhibitors; D007155:Immunologic Factors; D018697:Nootropic Agents; C558899:lopinavir-ritonavir drug combination; D061466:Lopinavir; D019438:Ritonavir
keywords: HIV; HIV protease inhibitor; Panax ginseng; antiretrovirals; complementary and alternative medicine; cytochrome P450; drug interaction; lopinavir-ritonavir; pharmacokinetics