Drug interaction between St John's wort and quazepam

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.