Drug interaction between St John's Wort and quazepam

British Journal of Clinical Pharmacology
Atsuhiro KawaguchiAkio Fujimura

Abstract

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. 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. SJW decreased the plasma quazepam concentration. The Cmax and AUC(0-48) 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 6beta-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, ...Continue Reading

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