title: Herb-Drug Pharmacokinetic Interactions: Transport and Metabolism of Indinavir in the Presence of Selected Herbal Products.
abstract: Patients receiving anti-retroviral drug treatment are sometimes simultaneously taking herbal remedies, which may result in pharmacokinetic herb-drug interactions. This study aimed to determine if pharmacokinetic interactions exist between selected commercially available herbal products (i.e., Linctagon Forte(®), Viral Choice(®) and Canova(®)) and indinavir in terms of in vitro transport and metabolism. Bi-directional transport of indinavir was evaluated across Caco-2 cell monolayers in the presence and absence of the selected herbal products and verapamil (positive control). Metabolism of indinavir was determined in LS180 cells in the presence and absence of the selected herbal products as well as ketoconazole (positive control). The secretory transport of indinavir increased in a concentration dependent way in the presence of Linctagon Forte(®) and Viral Choice(®) when compared to that of indinavir alone. Canova(®) only slightly affected the efflux of indinavir compared to that of the control group. There was a pronounced inhibition of the metabolism of indinavir in LS180 cells over the entire concentration range for all the herbal products investigated in this study. These in vitro pharmacokinetic interactions indicate the selected herbal products may affect indinavir's bioavailability, but the clinical significance needs to be confirmed with in vivo studies before final conclusions can be made.
authors.affiliation: Centre of Excellence for Pharmaceutical Sciences, North-West University, Private Bag X6001, Potchefstroom 2520, South Africa. 20743149@nwu.ac.za.
authors.forename: Carlemi
authors.initials: C
authors.lastname: Calitz
authors.affiliation: Centre of Excellence for Pharmaceutical Sciences, North-West University, Private Bag X6001, Potchefstroom 2520, South Africa. Chrisna.Gouws@nwu.ac.za.
authors.forename: Chrisna
authors.initials: C
authors.lastname: Gouws
authors.affiliation: Centre of Excellence for Pharmaceutical Sciences, North-West University, Private Bag X6001, Potchefstroom 2520, South Africa. 11320036@nwu.ac.za.
authors.forename: Joe
authors.initials: J
authors.lastname: Viljoen
authors.affiliation: Centre of Excellence for Pharmaceutical Sciences, North-West University, Private Bag X6001, Potchefstroom 2520, South Africa. Jan.Steenekamp@nwu.ac.za.
authors.forename: Jan
authors.initials: J
authors.lastname: Steenekamp
authors.affiliation: Department of Medicine, University of Cape Town, Observatory 7925, South Africa. lubbe.wiesner@uct.ac.za.
authors.forename: Lubbe
authors.initials: L
authors.lastname: Wiesner
authors.affiliation: Department of Medicine, University of Cape Town, Observatory 7925, South Africa. efrem.abay@uct.ac.za.
authors.forename: Efrem
authors.initials: E
authors.lastname: Abay
authors.affiliation: Centre of Excellence for Pharmaceutical Sciences, North-West University, Private Bag X6001, Potchefstroom 2520, South Africa. Sias.Hamman@nwu.ac.za.
authors.forename: Josias
authors.initials: J
authors.lastname: Hamman
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D019380:Anti-HIV Agents / Q000494:pharmacology*; D001692:Biological Transport; D018938:Caco-2 Cells; D045744:Cell Line, Tumor; D003435:Crotalid Venoms / Q000494:pharmacology*; D051544:Cytochrome P-450 CYP3A / Q000378:metabolism; D041743:Herb-Drug Interactions; D006801:Humans; D019469:Indinavir / Q000494:pharmacology*; D007654:Ketoconazole / Q000494:pharmacology; D010936:Plant Extracts / Q000494:pharmacology*; D014700:Verapamil / Q000494:pharmacology
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D019380:Anti-HIV Agents; C513575:Canova medication; D003435:Crotalid Venoms; D010936:Plant Extracts; D019469:Indinavir; D014700:Verapamil; D051544:Cytochrome P-450 CYP3A; D007654:Ketoconazole
keywords: Caco-2; LS180; P-glycoprotein; cytochrome P450; efflux; herb-drug interactions; metabolism