OBJECTIVE: St John's Wort, a widely used herbal product, is an inducer of CYP3A4 and it decreases blood concentrations of CYP3A4 substrates. The effects of St John's Wort on the pharmacokinetics of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors simvastatin (an inactive lactone pro-drug) and pravastatin were determined in this study. METHODS: Sixteen healthy male subjects (n = 8 in group 1 and n = 8 in group 2) took a St John's Wort caplet (300 mg) or matching placebo three times a day for 14 days in a double-blind, crossover study. On day 14, a single oral dose of 10 mg simvastatin and 20 mg pravastatin was given to subjects in group 1 and group 2, respectively. Blood samples were obtained during a 24-hour period after the administration of each drug. RESULTS: Repeated St John's Wort treatment tended to lower plasma simvastatin concentration and significantly (P <.05) lowered concentrations of simvastatin hydroxy acid, its active metabolite. The peak concentration in plasma (ratio, 0.72 of placebo) of simvastatin hydroxy acid tended to be decreased and its area under the plasma concentration-time curve between time zero and 24 hours after administration (ratio, 0.48 of placebo) was significantly decreased (P <.05) by St John's Wort. On the other hand, St John's Wort did not influence plasma pravastatin concentration. No significant differences were observed in the elimination half-life of simvastatin or pravastatin between the placebo and St John's Wort trials. CONCLUSIONS: This study showed that St John's Wort decreases plasma concentrations of simvastatin but not of pravastatin. Because simvastatin is extensively metabolized by CYP3A4 in the intestinal wall and liver, which are induced by St John's Wort, it is likely that this interaction is partly caused by the enhancement of the CYP3A4-mediated first-pass metabolism of simvastatin in the small intestine and liver

Objective. To assess the effect of treatment with a St John's Wort product (Movina) on cholesterol levels (total cholesterol, LDL-cholesterol, and HDL-cholesterol) in patients with hypercholesterolemia on treatment with a stable dose of simvastatin. Design. Controlled, randomized, open, crossover pharmacodynamic study. Setting. Two primary healthcare centres. Intervention. Patients were treated with Movina one tablet (containing 300 mg of Hypericum perforatum) twice daily and control (a commercially available multivitamin tablet, Vitamineral). The trial started with a run-in period of 4 weeks. Then the treatment order between control and active treatment was decided (randomization using sealed envelopes). The duration of each treatment period was 4 weeks and simvastatin treatment was kept unchanged during the whole study period (12 weeks). Subjects. Twenty-four patients with hypercholesterolemia treated with a stable dose of simvastatin (10-40 mg daily) for at least three months. Main outcome measures. Assessments of total cholesterol, HDL- cholesterol, LDL-cholesterol, and triglycerides were performed in the morning with the patients in a fasting condition. Results. All patients completed the study. LDL-cholesterol was significantly increased during active treatment compared with control. Thus, the mean LDL-cholesterol after 4 weeks' active treatment was 2.72 mmol/L compared with 2.30 mmol/L after treatment with control (p <0.0001). An increase in total-cholesterol was also observed (5.08 mmol/L compared with 4.56 mmol/L, p <0.0001). Conclusion. Products containing St John's Wort should not be given to patients with hypercholesterolemia who are on treatment with simvastatin. copyright 2007 Taylor & Francis

OBJECTIVE: The aim of this study was to assess the effect of treatment with a St. John's wort product (Movina) on cholesterol [total cholesterol, low-density lipoprotein (LDL) cholesterol and high-density lipoprotein (HDL) cholesterol] and triglyceride levels in patients with hypercholesterolemia on treatment with a stable dose of atorvastatin in a controlled, randomised, open, crossover interaction study. METHODS: Sixteen patients with hypercholesterolemia treated with a stable dose of atorvastatin (10-40 mg/daily) for at least 3 months were treated with Movina one tablet (containing 300 mg of hypericum perforatum) twice daily and control (a commercially available multivitamin tablet Vitamineral). After a run-in period of 4 weeks, patients were randomised to treatment with either Movina or control for 4 weeks in a crossover design. The atorvastatin dose was kept unchanged during the study period (12 weeks), and assessments of total cholesterol, HDL cholesterol, LDL cholesterol and triglycerides were performed in the morning with the patients in the fasting condition. The difference between control and active treatment in LDL cholesterol after 4 weeks of treatment was the primary endpoint. RESULTS: All patients completed the study. The St. John's wort product significantly increased the serum level of LDL cholesterol compared with control (2.66 mmol/l compared with 2.34 mmol/l, p = 0.004). A significant increase in total cholesterol was also observed (5,10 mmol/l compared with 4.78 mmol/l, p = 0.02). No statistically significant change was observed in HDL cholesterol (1.59 mmol/l and 1.56 mmol/l, p = 0.49) or in triglycerides (1.87 mmol/l and 1.94 mmol/l, p = 0.60). No product-related side effects were reported CONCLUSION: An interaction was observed between the studied St.-John's-wort-containing product and atorvastatin. Physicians and patients should be aware of this interaction and if treatment with a St. John's wort product is considered necessary, then there may be a need for increasing the dose of atorvastatin

Despite the widespread use of herbal medicines, documented herb-drug interactions are sparse. We have reviewed the literature to determine the possible interactions between the seven top-selling herbal medicines (ginkgo, St John´s wort, ginseng, garlic, echinacea, saw palmetto and kava) and prescribed drugs. Literature searches were performed using the following databases: Medline (via Pubmed), Cochrane Library, Embase and phytobase (all from their inception to July 2000). All data relating to herb-drug interactions were included regardless of whether they were based on case reports, case series, clinical trials or other types of investigation in humans. In vitro experiments were excluded. Data were extracted by the first author and validated by the second author. 41 case reports or case series and 17 clinical trials were identified. The results indicate that St John´s wort (Hypericum perforatum) lowers blood concentrations of cyclosporin, amitriptyline, digoxin, indinavir, warfarin, phenprocoumon and theophylline; furthermore it causes intermenstrual bleeding, delirium or mild serotonin syndrome, respectively, when used concomitantly with oral contraceptives (ethinylestradiol/desogestrel), loperamide or selective serotonin-reuptake inhibitors (sertaline, paroxetine, nefazodone). Ginkgo (Ginkgo biloba) interactions include bleeding when combined with warfarin, raised blood pressure when combined with a thiazide diuretic and coma when combined with trazodone. Ginseng (Panax ginseng) lowers blood concentrations of alcohol and warfarin, and induces mania if used concomitantly with phenelzine. Garlic (Allium sativum) changes pharmacokinetic variables of paracetamol, decreases blood concentrations of warfarin and produces hypoglycaemia when taken with chlorpropamide. Kava (Piper methysticum) increases ´off´ periods in Parkinson patients taking levodopa and can cause a semicomatose state when given concomitantly with alprazolam. No interactions were found for echinacea (Echinacea angustifolia, E. purpurea, E. pallida) and saw palmetto (Serenoa repens). In conclusion, interactions between herbal medicines and synthetic drugs exist and can have serious clinical consequences. Healthcare professionals should ask their patients about the use of herbal products and consider the possibility of herb-drug interactions