HERBAL INHIBITION OF BETA GLUCURONIDASE IN FECES OF NORMAL VOLUNTEERS: PHASE i

University Of Wisconsin Madison, Madison WI

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Abstract

The purpose of this study is to determine the oral dose of silymarin required to inhibit the beta-glucuronidase activity in feces, and also to determine the lag time between dosing and the enzyme inhibition. Dose escalation is planned not to seek toxicity, which is considered unlikely, but to determine the "effective" dose that will cause a 50% reduction in beta-glucuronidase activity. Blood concentrations of silybin, the primary constituent of silymarin, will be tested to assist in the characterization of the pharmacokinetics of this compound. This trial in normal adult volunteers is a Phase I/II study performed prior to a planned Phase II that will determine whether prophylactic administration of silymarin can decrease the dose-limiting diarrhea commonly encountered in patients receiving the camptothecin drug irinotecan (CPT-11). The silybin is postulated to decrease the diarrhea by blocking bacterial beta-glucuronidases in the gut and preventing the reactivation of the SN38-glucuronide back to the active form SN38. "