Drug interaction between St John’s wort and zolpidem in healthy subjects

Department of Neuropsychiatry, Bioregulatory Medicine, Akita University Graduate School of Medicine, Akita, Japan.
Journal of Clinical Pharmacy and Therapeutics (Impact Factor: 1.67). 11/2010; 36(6):711-5. DOI: 10.1111/j.1365-2710.2010.01223.x
Source: PubMed


St John's wort (SJW, Hypericum perforatum) is one of the most commonly used herbal antidepressants for treatment of mild to moderate depression. SJW enhances CYP3A4 activity and alters the pharmacokinetics of CYP3A4 substrates. This study investigated the effect of SJW on the pharmacokinetics of zolpidem in healthy subjects.
A controlled, open-label, non-randomized, fixed-dose schedule design was used. Fourteen healthy male subjects received a single 10 mg oral dose of zolpidem followed by SJW administration (300 mg orally, three times a day) for 14 days; the last dose of SJW was coadministered with a single dose of zolpidem. Blood samples were obtained over a 24-h period after zolpidem administration. Pharmacokinetic data for zolpidem alone and in combination with SJW were analysed by high-performance liquid chromatography. Results: After repeated administration of SJW, the mean values of AUC and C(max) for zolpidem significantly decreased (380.3 ± 181.4 vs. 265.4 ± 134.2 ng h/mL, P = 0.001; 83.1 ± 30.1 vs. 55.1 ± 24.8 ng/mL, P = 0.000 respectively) and the mean value of CL/F for zolpidem significantly increased (38.4 ± 31.5 vs. 56.9 ± 57.2 mL/min, P = 0.040). However, in three subjects, the AUC showed a small increase after SJW treatment.
The effect of SJW on the pharmacokinetics of zolpidem has not previously been reported. Repeated administration of SJW decreases the plasma concentration of zolpidem, probably by enhancing CYP3A4 activity. Given the wide inter-subject variability observed, for personalized medicine, advice on the use of the combination should be individualized, based on the circumstances of the patient.

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    • "However, in 3 out of 14 subjects, a slight increase in the CYP plasma concentration was reported. Zolpidem is mainly metabolized by CYP3A4[100]. "
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    ABSTRACT: INTRODUCTION: Hypericum perforatum (HP), more commonly known as St. John's wort, is a popular medicinal herb used for the treatment of depression. HP affects the pharmacokinetics of many drugs by inducing cytochrome P450 (CYP) isozymes, such as CYP3A4, CYP2C19, CYP2C9, and the P-glycoprotein (P-gp) transporter. AREAS COVERED: This review focuses on drugs that are metabolized by CYP3A4, CYP2C19, CYP2C9 and P-gp as their plasma concentrations show the effects of concomitant use of HP. For the purpose of this review, all electronic databases such as PubMed, Scopus, Google Scholar and Cochrane library were searched to identify in vitro, in vivo or human studies about the effects of HP on the metabolism of drugs. Data collected were published between 1966 and January 2012. EXPERT OPINION: There are a number of drugs whose metabolism is reduced by HP. The authors point out that metabolic interactions between HP and drugs are not always unfavorable and sometimes have benefits (e.g., reduction of irinotecan toxicity and increase in clopidogrel responsiveness). HP does not have a significant influence on the kinetics of drugs such as carbamazepine, ibuprofen and theophylline. The use of HP preparations is not recommended in people who are taking immunosuppressants or cardiovascular drugs. With other medications, it is recommended that practitioners should only use HP preparations with a low hyperforin content and under careful monitoring. It is also recommended that because of the reduction in the bioavailability of oral contraceptives administered concurrently with HP, women who use HP preparations should use additional preventive methods to avoid unintended pregnancy.
    Preview · Article · Jun 2012 · Expert Opinion on Drug Metabolism & Toxicology
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    ABSTRACT: This article provides an overview of the clinical evidence of interactions between herbal and conventional medicines. Herbs involved in drug interactions--or that have been evaluated in pharmacokinetic trials--are discussed in this review. While many of the interactions reported are of limited clinical significance and many herbal products (e.g. black cohosh, saw palmetto, echinacea, hawthorn and valerian) seem to expose patients to minor risk under conventional pharmacotherapy, a few herbs, notably St. John's wort, may provoke adverse events sufficiently serious to endanger the patients' health. Healthcare professionals should remain vigilant for potential interactions between herbal medicines and prescribed drugs, especially when drugs with a narrow therapeutic index are used.
    No preview · Article · Jan 2012 · Medical Principles and Practice
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