Drug interaction between St John's Wort and quazepam

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Abstract
Aim: St John's Wort (SJW) enhances CYP3A4 activity and decreases blood concentrations of CYP3A4 substrates. In this study, the effects of SJW on a benzodiazepine hypnotic, quazepam, which is metabolized by CYP3A4, were examined.Methods: Thirteen healthy subjects took a single dose of quazepam 15 mg after treatment with SJW (900 mg day−1) or placebo for 14 days. The study was performed in a randomized, placebo‐controlled, cross‐over design with an interval of 4 weeks between the two treatments. Blood samples were obtained during a 48 h period and urine was collected for 24 h after each dose of quazepam. Pharmacodynamic effects were determined using visual analogue scales (VAS) and the digit symbol substitution test (DSST) on days 13 and 14.Results: SJW decreased the plasma quazepam concentration. The Cmax and AUC0‐48 of quazepam after SJW were significantly lower than those after placebo [Cmax; −8.7 ng ml−1 (95% confidence interval (CI) −17.1 to −0.2), AUC0‐48; −55 ng h ml−1 (95% CI −96 to −15)]. The urinary ratio of 6β‐hydroxycortisol to cortisol, which reflects CYP3A4 activity, also increased after dosing with SJW (ratio; 2.1 (95%CI 0.85–3.4)). Quazepam, but not SJW, produced sedative‐like effects in the VAS test (drowsiness; P < 0.01, mental slowness; P < 0.01, calmness; P < 0.05, discontentment; P < 0.01). On the other hand, SJW, but not quazepam impaired psychomotor performance in the DSST test. SJW did not influence the pharmacodynamic profile of quazepam.Conclusions: These results suggest that SJW decreases plasma quazepam concentrations, probably by enhancing CYP3A4 activity, but does not influence the pharmacodynamic effects of the drug.