Induction and recovery of hepatic drug metabolizing enzymes in rats treated with Ginkgo biloba extract

Herb-drug interactions, especially cytochrome P450 (CYP)-mediated interactions, cause an enhancement or attenuation in efficacy of co-administered drugs. In a previous study, we reported that repeated oral ingestion of Ginkgo biloba extract (GBE) markedly induced hepatic drug metabolizing enzymes in rats (Jpn. J. Pharmacol. 90, 345-351, 2002). In this study, we focused on the recovery of GBE-induced hepatic drug metabolizing enzymes after the discontinuation of GBE in rats. Feeding of a 0.5% GBE diet to rats for 1 week markedly increased liver weight, content of total CYP, activities of 6 CYP subtypes and glutathione S-transferase (GST). The content and activities of CYP enzymes were recovered to almost basal levels within 1 week after the discontinuation of GBE, while the activity of GST gradually decreased and recovered to the control level after 3 weeks. These results indicated that GBE-induced hepatic drug metabolizing enzymes in rats, especially CYPs, were rapidly recovered by discontinuation of GBE in rats even after excess treatment, and suggested that interactions of GBE with drugs could be avoided by discontinuation of GBE. (C) 2004 Elsevier Ltd. All rights reserved.