Effects of Ginkgo biloba extract on the pharmacokinetics of bupropion in healthy volunteers

center dot Bupropion, an antidepressant and smoking cessation drug, is metabolized to its active metabolite hydroxybupropion almost exclusively by CYP2B6. center dot Ginkgo biloba is among the most commonly used herbal extract in the general population, and is likely to be used by depressed patients receiving bupropion. center dot Studies have reported that G. biloba administration to rats markedly increased the CYP content and CYP2B mRNA in the liver, and intake of G. biloba also induced various hepatic CYP enzymes, especially CYP2B-type enzymes. center dot There may be drug interactions between G. biloba extract and bupropion (CYP2B6 substrate). WHAT THIS STUDY ADDS center dot Fourteen-day oral administration of G. biloba extract had no statistically significant effect on the pharmacokinetics of bupropion or its active metabolite hydroxybupropion, as measured by AUC, which suggests G. biloba does not significantly affect the metabolism of bupropion following a single oral dose in healthy Chinese men. AIMS To assess the effects of Ginkgo biloba extract on the pharmacokinetics of bupropion in healthy volunteers. METHODS Fourteen healthy male volunteers (age range 19-25 years) received orally administered bupropion (150 mg) alone and during treatment with G. biloba 240 mg day(-1) (two 60-mg capsules taken twice daily) for 14 days. Serial blood samples were obtained over 72 h after each bupropion dose, and used to derive pharmacokinetic parameters of bupropion and its CYP2B6-catalysed metabolite, hydroxybupropion. RESULTS Ginkgo biloba extract administration resulted in no significant effects on the AUC(0-infinity) of bupropion and hydroxybupropion. Bupropion mean AUC(0-infinity) value was 1.4 mu g center dot h ml(-1) [95% confidence interval (CI) 1.2, 1.6] prior to G. biloba treatment and 1.2 mu g center dot h ml(-1) (95% CI 1.1, 1.4) after 14 days of treatment. Hydroxybupropion mean AUC(0-infinity) value was 8.2 mu g center dot h ml(-1) (95% CI 6.5, 10.4) before G. biloba administration and 8.7 mu g center dot h ml(-1) (95% CI 7.1, 10.6) after treatment. The C(max) of hydroxybupropion increased from 221.8 ng ml(-1) (95% CI 176.6, 278.6) to 272.7 ng ml(-1) (95% CI 215.0, 345.8) (P = 0.038) and the t(1/2) of hydroxybupropion fell from 25.0 h (95% CI 22.7, 27.5) to 21.9 h (95% CI 19.9, 24.1) (P = 0.000). CONCLUSIONS Ginkgo biloba extract administration for 14 days does not significantly alter the basic pharmacokinetic parameters of bupropion in healthy volunteers. Although G. biloba extract treatment appears to reduce significantly the t(1/2) and increase the C(max) of hydroxybupropion, no bupropion dose adjustments appear warranted when the drug is administered orally with G. biloba extract, due to the lack of significant change observed in AUC for either bupropion or hydroxybupropion.