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Effect of St. John’s wort supplementation on the pharmacokinetics of bupropion in healthy male Chinese volunteers

The objective of this study was to investigate the effects of continuous St. John’s wort administration on single-dose pharmacokinetics of bupropion, a substrate of cytochrome P450 (CYP) 2B6, in healthy Chinese volunteers. Eighteen unrelated healthy male subjects participated in this study. The single-dose pharmacokinetics of bupropion and hydroxybupropion were determined before (control) and after a long-term period of St. John’s wort intake (325 mg, three times a day for 14 days). Plasma concentrations of bupropion and hydroxybupropion were determined before and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 60 and 72 h after dosing. St. John’s wort treatment decreased the area under the concentration versus time curve extrapolated to infinity of bupropion in healthy volunteers from 1.4 μg·h ml−1 (95% confidence interval [CI] = 1.2–1.6 μg·h ml−1) after bupropion alone to 1.2 μg·h ml−1 (95% CI = 1.1–1.3 μg·h ml−1) during St. John’s wort treatment. St. John’s wort treatment increased the oral clearance of bupropion from 108.3 l h−1 (95% CI = 95.4–123.0 l h−1) to 130.0 l h−1 (95% CI = 118.4–142.7 l h−1). No change in the time to peak concentration (tmax) and the blood elimination half-life (t1/2) of bupropion was observed between the control and St. John’s wort-treated phases. However, the half-life of hydroxybupropion between two phases had a significant difference by a Student’s t test after logarithmic transformation. St. John’s wort treatment decreased the half-life of hydroxybupropion from 26.7 h (95% CI = 23.8–29.9 h) to 24.4 h (95% CI = 21.9–27.3 h). St. John’s wort decreased, to a statistically significant extent, the plasma concentrations of bupropion, probably mainly by increasing the clearance of bupropion.