title: Drug interaction between St John's Wort and quazepam.
abstract: OBJECTIVE
  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 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, 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.
authors.affiliation: Department of Clinical Pharmacology, Jichi Medical School, Tochigi, Japan.
authors.forename: Atsuhiro
authors.initials: A
authors.lastname: Kawaguchi
authors.forename: Masami
authors.initials: M
authors.lastname: Ohmori
authors.forename: Shu-Ichi
authors.initials: S
authors.lastname: Tsuruoka
authors.forename: Kenta
authors.initials: K
authors.lastname: Nishiki
authors.forename: Kenichi
authors.initials: K
authors.lastname: Harada
authors.forename: Isamu
authors.initials: I
authors.lastname: Miyamori
authors.forename: Ryo-Ichi
authors.initials: R
authors.lastname: Yano
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Nakamura
authors.forename: Mikio
authors.initials: M
authors.lastname: Masada
authors.forename: Akio
authors.initials: A
authors.lastname: Fujimura
mesh_terms: D000328:Adult; D001569:Benzodiazepines / Q000378:metabolism* / Q000494:pharmacology; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004347:Drug Interactions; D006801:Humans; D020902:Hypericum / Q000378:metabolism*; D006993:Hypnotics and Sedatives / Q000378:metabolism* / Q000494:pharmacology; D008297:Male
chemical_list: D006993:Hypnotics and Sedatives; D001569:Benzodiazepines; C025130:quazepam