Effects of mistletoe products on pharmacokinetic drug turnover by inhibition and induction of cytochrome P450 activities

BACKGROUND: European mistletoe (Viscum album) products used in cancer therapy are frequently combined with other anti-cancer-drugs. Hence, potential herb-drug interactions have become a major safety concern in mistletoe therapy. METHODS: Three European mistletoe products (Helixor® A, Helixor® M and Helixor® P from mistletoe grown on firs, apple trees and pines, respectively) were tested for inhibition of nine major cytochrome P450 (CYP) isoenzymes in a test system using pooled human liver microsomes and for induction of five CYP isoforms in human hepatocytes cultivated in vitro according to the relevant guideline. RESULTS: Major inhibition did not occur in any of the CYP marker reactions. For some CYP isoenzymes, a minor or intermediate inhibition could be observed, but without dose effect relationship. Induction activity (≥ 1.5-fold increase) was not found with any of the three mistletoe products. CONCLUSION: Since no induction capacity was found and major inhibition above 50% did not occur even with the highest concentration used, which is approximately 100,000-fold higher than the clinically relevant dose in plasma, a clinically relevant herb-drug interaction is not expected for Helixor® A, M, and P.