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Drug interaction between St John's Wort and quazepam
Author(s) -
Kawaguchi Atsuhiro,
Ohmori Masami,
Tsuruoka Shuichi,
Nishiki Kenta,
Harada Kenichi,
Miyamori Isamu,
Yano Ryoichi,
Nakamura Toshiaki,
Masada Mikio,
Fujimura Akio
Publication year - 2004
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/j.1365-2125.2004.02171.x
Subject(s) - placebo , pharmacodynamics , pharmacology , benzodiazepine , hypnotic , digit symbol substitution test , pharmacokinetics , cyp3a4 , medicine , midazolam , cytochrome p450 , sedation , metabolism , alternative medicine , receptor , pathology
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 C max and AUC 0‐48 of quazepam after SJW were significantly lower than those after placebo [ C max ; −8.7 ng ml −1 (95% confidence interval (CI) −17.1 to −0.2), AUC 0‐48 ; −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.