Milk thistle ([MT] Silybum marianum) has been utilized for centuries as a natural remedy for various diseases affecting the liver and biliary tract. It is typically utilized as a concentrated extract derived from the seeds of the MT plant and standardized to a concentration of 70 to 80% of four flavonoid derivatives (silybin A and B, silichristin, and silidianin), collectively referred to as silymarin. Numerous clinical studies have been performed to date assessing various MT formulations for a variety of hepatic disorders. Despite some limitations and methodological flaws MT treatment appears to offer some potential as a treatment for a number of hepatic ailments. However, more rigorous clinical studies are needed. Additionally, a number of in vitro studies have attributed unique and potentially therapeutic biochemical attributes to the parent (i.e. non-conjugated) silybins. At present, there is a dearth of information available relative to the clinical pharmacokinetics of the active MT constituents as well as the drug interaction potential of MT supplements orally ingested by the lay public and potentially, clinical patients. To date, no study assessing MT for a therapeutic indication has also measured silybin isomer concentrations in plasma in a meaningful way. We propose, in a series of studies utilizing our institution's GCRC, to characterize the clinical pharmacokinetics of the 4 major constituents in normal volunteers dosed with a standardized and characterized silymarin supplement as well as to perform a botanical drug interaction study utilizing accepted probe drug methodology in normal volunteers. Foundational studies such as these are required in order to adequately design further clinical trials. Specific Aim 1: To determine the bioavailability and overall pharmacokinetics of the major biologically active MT constituents in a standardized MT supplement after consumption of a single MT supplement dose at three different dosage levels and an ensuing steady-state dosing pharmacokinetic assessment. Specific Aim 2: To determine the potential of a standard MT supplement to participate in drug interactions by assessing its ability to induce/inhibit CYP3A4, CYP2D6, CYP2C9 and CYP1A2. Although fundamental to the appropriate design of any clinical trial, these pharmacokinetic characteristics of MT constituents are largely unknown. The proposed exploratory studies will provide a foundational basis for the design of clinical studies allowing the appropriate choice of formulation, dosages and dosing schedules of MT supplements. Further, the important issues of concomitant pharmacotherapy and drug interactions will be addressed.