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Drug interaction between St John's Wort and quazepam
Atsuhiro Kawaguchi1, Masami Ohmori, Shu-Ichi Tsuruoka
1Department of Clinical Pharmacology, Jichi Medical School, Tochigi, Japan.
British Journal of Clinical Pharmacology
|September 18, 2004
Summary
St. John's Wort (SJW) reduces blood levels of the hypnotic drug quazepam by increasing CYP3A4 enzyme activity. However, SJW does not alter the sedative effects of quazepam, despite impacting psychomotor performance independently.
Area of Science:
- Pharmacology
- Herbal Medicine Interactions
- Drug Metabolism
Background:
- St. John's Wort (SJW) is known to induce CYP3A4 enzyme activity.
- CYP3A4 plays a crucial role in metabolizing numerous drugs, including benzodiazepines.
- Quazepam is a benzodiazepine hypnotic metabolized by CYP3A4.
Purpose of the Study:
- To investigate the effect of St. John's Wort (SJW) on the pharmacokinetics and pharmacodynamics of quazepam.
- To determine if SJW alters quazepam plasma concentrations due to its known effect on CYP3A4 activity.
Main Methods:
- A randomized, placebo-controlled, cross-over study involving 13 healthy subjects.
- Subjects received 14 days of SJW (900 mg/day) or placebo, followed by a single 15 mg dose of quazepam.
- Plasma concentrations and urinary markers of CYP3A4 activity were measured; pharmacodynamic effects were assessed using VAS and DSST.
Main Results:
- SJW significantly reduced quazepam's maximum plasma concentration (Cmax) and area under the curve (AUC).
- The urinary ratio of 6beta-hydroxycortisol to cortisol, a marker of CYP3A4 activity, increased significantly after SJW administration.
- While quazepam caused sedation, SJW alone impaired psychomotor performance (DSST), but did not affect quazepam's pharmacodynamic profile.
Conclusions:
- St. John's Wort likely decreases plasma quazepam concentrations by inducing CYP3A4 activity.
- Despite altering quazepam levels, SJW does not appear to influence the drug's pharmacodynamic effects.
- This suggests a potential for altered therapeutic efficacy or safety profiles when combining SJW with quazepam.