In vitro inhibitory effects of herbal supplements on tamoxifen and irinotecan metabolism.

BACKGROUND: As the use of herbal supplements continues to rise throughout the world, the potential for drug-herbal interactions also increases. For chemotherapeutic prodrugs, this interaction could prevent the metabolic conversion of the prodrug to its active metabolite(s), thereby potentially resulting in subtherapeutic systemic exposure of the drug and reduced efficacy of the therapy.

METHODS: In this study, in vitro metabolism with human liver microsomes is used to measure the impact of ten commonly used herbal supplements on the biotransformation of the chemotherapeutic prodrugs tamoxifen (TAM) and irinotecan (IR).

RESULTS: Four of the herbals tested, echinacea, ginseng, lemon balm, and skullcap, were found to be strong inhibitors of the CYP450 enzymatic bioactivation pathways of TAM with IC50 values as percent of a single dose ranging from 0.019% to 0.34%. Two of the herbals, skullcap and lemon balm, were found to inhibit the carboxyesterase pathway of IR with values of 0.21 and 0.25, respectively.

CONCLUSIONS: Our data suggests that based on the measured IC50 values that skullcap and lemon balm could have potential negative clinical impact on the bioactivation of TAM but not likely with IR.