Influence of Panax ginseng on the Steady State Pharmacokinetic Profile of Lopinavir-Ritonavir in Healthy Volunteers M onica M. Calder on,1,4 Cheryl L. Chairez,2 Lori A. Gordon,1 Raul M. Alfaro,1 Joseph A. Kovacs,3 and Scott R. Penzak1,* 1
Clinical Research Center, Clinical Center Pharmacy Department, National Institutes of Health, Bethesda, Maryland; 2National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland; 3Clinical Research Center, Department of Critical Care Medicine, National Institutes of Health, Bethesda, Maryland; 4Current address: Office of Safety and Epidemiology, U.S. Food and Drug Administration, Silver Spring, Maryland
STUDY 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. DESIGN Single-sequence, open-label, single-center pharmacokinetic investigation. SETTING Government health care facility. SUBJECTS Twelve healthy human volunteers. MEASUREMENTS AND MAIN 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
Clinical Research Center, Clinical Center Pharmacy Department, National Institutes of Health, Bethesda, Maryland; 2National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland; 3Clinical Research Center, Department of Critical Care Medicine, National Institutes of Health, Bethesda, Maryland; 4Current address: Office of Safety and Epidemiology, U.S. Food and Drug Administration, Silver Spring, Maryland
STUDY 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. DESIGN Single-sequence, open-label, single-center pharmacokinetic investigation. SETTING Government health care facility. SUBJECTS Twelve healthy human volunteers. MEASUREMENTS AND MAIN 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
