The Influence of St. John’s Wort on CYP2C19 Activity with Respect to Genotype

Pharmacogenetics Research Institute, Institute of Clinical Pharmacology, Central South University, Changsha, Hunan 410078, China.
The Journal of Clinical Pharmacology (Impact Factor: 2.48). 06/2004; 44(6):577-581. DOI: 10.1177/0091270004265642
Source: PubMed


Induction of cytochrome P450 isozymes is the major cause for clinical drug interactions of St. John’swort. The relationships of St. John’swort to cytochrome P450 isoforms have been fully investigated, but its effect on CYP2C19 is lacking. Thus, the aim ofthe present study was to observe the effect of St. John’s wort on CYP2C19 activity using CYP1A2 as a control. Twelve healthy adult men—6 extensive metabolizers of CYP2C19 (2C19*1/2C19*1) and 6 poor metabolizers (42C19*2/2C19*2 and 22C19*2/2C19*3) —were enrolled in a twophase, randomized, crossover manner. All subjects took a 300-mg St. John’swort tablet or placebo three times daily for 14 days, and then the activities of CYP2C19 and CYP1A2 were measured using mephenytoin and caffeine. It was found that St. John’s wort treatment significantly increased CYP2C19 activity in CYP2C19 wild-genotype subjects, with urinary 4 -hydroxymephenytoin excretion raised by 151.5%±91.9% (p = 0.0156), whereas no significant alteration was observed for CYP2C19 poor metabolizers. Repeated St. John’s wort administration did not affect the CYP1A2 phenotypic ratio for both CYP2C19 genotype subjects. In conclusion, St. John’s wort is an inducer to the human CYP2C19, and clinicians should pay great attention when St. John’s wort is added to or withdrawn from an existing drug regimen containing substrates for such enzymes.

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    ABSTRACT: Hypericum perforatum (HP) belongs to the Hypericaceae family and is one of the oldest used and most extensively investigated medicinal herbs. The medicinal form comprises the leaves and flowering tops of which the primary ingredients of interest are naphthodianthrones, xanthones, flavonoids, phloroglucinols (e.g. hyperforin), and hypericin. Although several constituents elicit pharmacological effects that are consistent with HP's antidepressant activity, no single mechanism of action underlying these effects has thus far been found. Various clinical trials have shown that HP has a comparable antidepressant efficacy as some currently used antidepressant drugs in the treatment of mild/moderate depression. Interestingly, low-hyperforin-content preparations are effective in the treatment of depression. Moreover, HP is also used to treat certain forms of anxiety. However, HP can induce various cytochrome P450s isozymes and/or P-glycoprotein, of which many drugs are substrates and which are the main origin of HP-drug interactions. Here, we analyse the existing evidence describing the clinical consequence of HP-drug interactions. Although some of the reported interactions are based on findings from in vitro studies, the clinical importance of which remain to be demonstrated, others are based on case reports where causality can, in some cases, be determined to reveal clinically significant interactions that suggest caution, consideration, and disclosure of potential interactions prior to informed use of HP. Copyright © 2013 John Wiley & Sons, Ltd.
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