Inhibition of Paclitaxel Metabolism In Vitro in Human Hepatocytes by Ginkgo biloba Preparations

摘要

Since the late 1980s, chemotherapy-induced cognitive impairment, also known as "chemobrain", has been a recognized side effect in patients undergoing cancer treatment (Matsuda et al., 2005). Although products containing Ginkgo biloba may be used by patients undergoing chemotherapy with paclitaxel and other agents, the potential for an herb-drug interaction with this combination has not been adequately explored. This report describes the inhibition of paclitaxel metabolism by Ginkgo preparations in vitro in human hepatocytes. Hydrolyzate of Ginkgo extract (10-100 mM in terpene lactone concentration) caused a dose-dependent inhibition of the 6alpha-hydroxylation of paclitaxel, the enzymatic activity responsible for the majority of the clearance of that drug in clinical applications; parent extract had no effect. Contrary to the assumed therapeutic benefit of Ginkgo, its concomitant use with paclitaxel could result in elevated blood levels of the chemotherapeu-tic, with attendant exacerbation of cognitive impairment and other toxic effects associated with cancer therapy.