Interactions between natural health products and antiretroviral drugs: pharmacokinetic and pharmacodynamic effects.
Concurrent use of natural health products (NHPs) with antiretroviral drugs (ARVs) is widespread among human immunodeficiency virus-infected patients. This article reviews the clinical pharmacokinetic and pharmacodynamic interactions between NHPs and ARVs. Many NHPs are complex mixtures and are likely to contain organic compounds that may induce and/or inhibit drug metabolizing enzymes and drug transporters. Although the weight of evidence for the effects of certain NHPs varies and many studies of these products lack scientific rigor, it has been observed that St. John's wort clearly induces cytochrome P450 3A4 and P-glycoprotein and reduces protease inhibitor and nonnucleoside reverse-transcriptase inhibitor concentrations, thereby increasing the likelihood of therapeutic failure. Limited clinical research suggests that intake of garlic and vitamin C results in reductions in ARV concentrations. The intake of milk thistle, Echinacea species, and goldenseal inhibits cytochrome P450 enzymes in vitro and may increase ARV concentrations, but by clinically unimportant amounts. Intake of fish oil reduces ARV-induced hypertriglyceridemia without significantly affecting lopinavir concentrations. Before recommending the use of NHPs as adjuncts to ARV use, studies should first exclude significant pharmacokinetic interactions and ensure that ARV efficacy is maintained.
Lee
Lawrence S
LS
Division of Clinical Pharmacology, Johns Hopkins University, Baltimore, MD, USA.
Andrade
Adriana S A
AS
Flexner
Charles
C
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000187:drug effects; D044966:Anti-Retroviral Agents / Q000493:pharmacokinetics*; D001682:Biological Availability; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D014453:Glucuronosyltransferase / Q000378:metabolism; D041743:Herb-Drug Interactions; D006801:Humans; D010936:Plant Extracts / Q000493:pharmacokinetics; D010946:Plants, Medicinal
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D044966:Anti-Retroviral Agents; D010936:Plant Extracts; D003577:Cytochrome P-450 Enzyme System; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; D014453:Glucuronosyltransferase