Multifaceted interaction of the traditional Chinese medicinal herb Schisandra chinensis with cytochrome P450-mediated drug metabolism in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Schisandra chinensis (SC), officially listed as a sedative and tonic in the Chinese Pharmacopoeia, has been used as a common component in various prescriptions in Traditional Chinese Medicine (TCM) and more recently in western medicine for its antihepatotoxic effect. To assess the possible herb-drug interaction, effects of SC extracts on hepatic cytochrome P450 (P450, CYP) enzymes were studied. MATERIAL AND METHODS: Effects of SC extracts on rat hepatic CYP450 enzymes in vitro and in vivo were investigated by probe substrates method, real-time RT-PCR assay and Western blotting analysis. Furthermore, the effects of SC alcoholic extract on the PK of four SC lignans and the drugs possibly co-administrated in vivo were studied in male Sprague-Dawley rat. RESULTS: SC aqueous extract and alcoholic extract showed significant inhibitory effect on the activities of rat liver microsomal CYP1A2, 2C6, 2C11, 2D2, 2E1 and 3A1/2 in vitro. Multiple administrations of SC aqueous extract (1.5g/kg, qd×7d) and alcoholic extract (1.5g/kg, qd×7d) increased the activities, mRNA and protein expressions of CYP2E1 and CYP3A1/2, and meanwhile, inhibited the activities and mRNA expression of CYP2D2 in vivo. The in vivo metabolism of four SC lignans, such as schisandrin, schisantherin A, deoxyshisandrin and γ-schisandrin, and chlorzoxazone was significantly accelerated, exhibited by the reduced AUC and increased CLz/F, by 7-day pretreatment with SC alcoholic extract. However, both single and multiple dosing treatments of SC alcoholic extract remarkably decreased the in vivo metabolism of tacrolimus indicated by the enhanced AUC (7-12 fold) and elevated Cmax (10 fold). CONCLUSION: These results revealed that the SC extracts exhibited multifaceted effects on rat hepatic CYP450 enzymes. Herb-drug interaction should be paid intense attention between SC components and drugs metabolized by different CYP450 enzymes.

Evaluation of the pharmacokinetics, safety and clinical efficacy of sertraline used to treat social anxiety.

INTRODUCTION: Social anxiety disorder (SAD) is an emerging, often invalidating, syndrome with deep personal, social and psychological implications. While multiple treatment strategies exist, presently none of them can be considered superior to all others. AREAS COVERED: The aim of this review is to provide the latest information on sertraline (SRT), one of the most important selective serotonin reuptake inhibitors (SSRIs) currently used for the pharmacological therapy of SAD. A literature search was carried out with the keywords 'sertraline', 'social anxiety', 'social phobia' and 'clinical trials'. In this process, particular attention is paid to the pharmacokinetic characteristics of the drug and its safety in clinical use. EXPERT OPINION: SRT is an effective drug in the treatment of SAD, especially when used in combination with some form of psychological support. While it does not seem to be significantly more effective than other SSRIs, SRT could offer some peculiar advantages: for example, it has a long half-life, allowing a single daily administration, and seems to be particularly indicated for the control of specific symptoms of SAD.

Recurrent relapses of depression in a patient established on sertraline after taking herbal medicinal mixtures--a herb-drug interaction?

We describe a patient with depression who was well controlled with sertraline monotherapy developing two relapses of depression in close temporal relationship with starting ayurvedic herbal mixtures. We discuss the possibility of a pharmacokinetic herb-drug interaction decreasing the therapeutic efficacy of sertraline leading to the relapses of depression. We speculate the herbal plant most likely to be responsible for this interaction is either Terminalia chebula or Commiphora wighteii.