title: Inhibition of paclitaxel metabolism in vitro in human hepatocytes by Ginkgo biloba preparations.
abstract: 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 6α -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 chemotherapeutic, with attendant exacerbation of cognitive impairment and other toxic effects associated with cancer therapy.
authors.affiliation: Drug Metabolism & Pharmacokinetics, RTI International, Research Triangle Park, North Carolina 27709, USA.
authors.forename: Amy S
authors.initials: AS
authors.lastname: Etheridge
authors.forename: David J
authors.initials: DJ
authors.lastname: Kroll
authors.forename: James M
authors.initials: JM
authors.lastname: Mathews
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000009:adverse effects / Q000378:metabolism* / Q000627:therapeutic use; D003072:Cognition Disorders / Q000209:etiology; D004305:Dose-Response Relationship, Drug; D020441:Ginkgo biloba / Q000009:adverse effects*; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism; D041743:Herb-Drug Interactions; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy*; D017239:Paclitaxel / Q000009:adverse effects / Q000378:metabolism* / Q000627:therapeutic use; D028321:Plant Preparations / Q000009:adverse effects*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D028321:Plant Preparations; D017239:Paclitaxel