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At least 1,117 records · Page 62Linked to original sources
PubMed2004

Interaction of St John's wort with conventional drugs: systematic review of clinical trials.

OBJECTIVE: To determine the methodological quality of clinical trials that examined possible interactions of St John's wort with conventional drugs, and to examine the results of these trials. DESIGN: Systematic review. DATA SOURCES: Electronic databases from inception to April 2004, reference lists from published reports, and experts in the field. STUDY SELECTION: Eligible studies were prospective clinical trials evaluating the pharmacokinetic effect of St John's wort on the metabolism of conventional drugs. DATA EXTRACTION: Two reviewers selected studies for inclusion and independently extracted data. DATA SYNTHESIS: 22 pharmacokinetic trials studied an average of 12 (SD 5) participants; 17 trials studied healthy volunteers and five studied patients. Most (17) studies used a "before and after" design; four studies used control groups other than the active group. Three studies randomised the sequence of administration or the participants to study arms or periods; three studies blinded participants or investigators. In 15 trials, investigators independently assayed the herb. Of 19 trials with available plasma data, three found no important interaction (change in area under the curve < 20%) and 17 found a decrease in systemic bioavailability of the conventional drug; in seven studies the 95% confidence interval excluded a decrease of < 20%. CONCLUSION: Clinicians and patients should beware of possible decreases in the systemic bioavailability of conventional drugs when taken concomitantly with St John's wort.

Area Under Curve↗
PubMed2003

Mild depression in general practice: time for a rethink?

Clinical studies, conducted chiefly in hospital settings, have demonstrated that antidepressant drug therapy is effective treatment for major depressive disorder of at least moderate severity, and that cognitive therapy is an effective alternative to antidepressants in mild to moderate major depression. However, few clinical trials have taken place in general practice, where the great majority of patients with depression are managed. Most such patients in this setting do not meet diagnostic criteria for major depression, and are often described more loosely as having 'mild depression'. Many are given an antidepressant, often as the first step in treatment. Here, we consider whether this is the optimal approach for adults with mild depression in general practice.

Depressive Disorder↗
PubMed2005

Effect of the St. John's wort constituent hyperforin on docetaxel metabolism by human hepatocyte cultures.

BACKGROUND AND PURPOSE: St. John's wort is a commonly used herbal medication that increases cytochrome P450 3A (CYP3A) activity. Because docetaxel is inactivated by CYP3A, we studied the effects of the St. John's wort constituent hyperforin on docetaxel metabolism in a human hepatocyte model. EXPERIMENTAL DESIGN: Hepatocytes, isolated from three donor livers, were exposed to hyperforin (0.1, 0.5, or 1.5 micromol/L) or rifampin (10 micromol/L) for 48 hours. After 48 hours, hyperforin- or rifampin-containing medium was replaced with medium containing 100 micromol/L docetaxel. After 1 hour, docetaxel metabolism was characterized by liquid chromatography-tandem mass spectrometry. Subsequent incubations characterized the specific cytochrome P450s that produced the docetaxel metabolites observed in hepatocyte incubations. RESULTS: Rifampin induced docetaxel metabolism 6.8- to 32-fold above docetaxel metabolism in control cultures. Hyperforin induced docetaxel metabolism in all three hepatocyte preparations. Hyperforin induction was dose-dependent and, at maximum, was 2.6- to 7-fold greater than that in controls. Docetaxel metabolites identified in rifampin- and hyperforin-treated hepatocyte preparations included the previously described tert-butyl-hydroxylated metabolite and two previously unidentified metabolites involving hydroxylation on the baccatin ring. CYP3A4 produced the tert-butyl-hydroxylated metabolite and the two ring-hydroxylated metabolites. CYP2C8 produced one of the newly described ring-hydroxylated metabolites. CONCLUSIONS: Exposure to the St. John's wort constituent hyperforin induces docetaxel metabolism in vitro. This implies that subtherapeutic docetaxel concentrations may result when docetaxel is administered to patients using St. John's wort on a chronic basis. The results also show induction of previously undescribed metabolic pathways for docetaxel, one of which may be analogous to the known 6-alpha-hydroxylation of paclitaxel by CYP2C8.

Aged↗
PubMed2006

[Complementary and alternative therapies for climacteric symptoms].

OBJECTIVE: Review on complementary and alternative therapies for climacteric symptoms. METHODS: Search for publications about complementary or alternative treatments for climacteric symptoms based on Cochrane Library and Medline (1966-2006) including the references from the identified clinical trials and reviews. RESULTS: Cimicifuga may influence climacteric symptoms, especially hot flushes. Results for phytoestrogens, hop and Salvia seem promising but are less convincing. St. John's wort is an option for the treatment of moderate depressive symptoms. Phytoestrogens seem to have some potential for the prevention of osteoporosis and cardiovascular diseases. Results for the influence of lifestyle on hot flushes are conflicting, but interventions have demonstrated their use for the prevention of osteoporosis and cardiovascular diseases. CONCLUSIONS: Lifestyle modifications, Cimicifuga and phytoestrogens may relieve climacteric symptoms. Phytoestrogens and Cimicifuga should not be given to breast cancer survivors.

Acupuncture↗
PubMedDate not supplied

St John's wort: a systematic review of adverse effects and drug interactions for the consultation psychiatrist.

St. John's wort is an herb commonly used in Europe for decades and more recently the topic of scientific investigation in this country. St. John's wort has been found more effective than placebo and equally as effective as tricyclic antidepressants in the short-term management of mild-to-moderate depression. Comparisons to selective serotonin reuptake inhibitors have provided equivocal data. While it is generally well tolerated in clinical use, there is accumulating evidence of significant interactions with drugs. This evidence-based presentation of the literature includes a brief description of pharmacodynamics and clinical applications, followed by a systematic review of adverse effects, toxicity, and drug interactions.

Depressive Disorder↗
PubMed2004

The influence of St John's Wort on CYP2C19 activity with respect to genotype.

Induction of cytochrome p450 isozymes is the major cause for clinical drug interactions of St. John's wort. The relationships of St. John's wort to cytochrome p450 isoforms have been fully investigated, but its effect on CYP2C19 is lacking. Thus, the aim of the 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 (4 2C19(*)2/2C19(*)2 and 2 2C19(*)2/2C19(*)3)-were enrolled in a two-phase, randomized, crossover manner. All subjects took a 300-mg St. John's wort 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.

Adult↗
PubMed2006

Investigation of the effects of herbal medicines on warfarin response in healthy subjects: a population pharmacokinetic-pharmacodynamic modeling approach.

Systematic evidence regarding herb-drug interactions is lacking. This study investigated herb-drug interactions with warfarin. S-warfarin concentration and response (prothrombin complex activity) data from healthy subjects (n = 24) who received a single warfarin dose (25 mg) and either St John's wort, Asian ginseng, Ginkgo biloba, or ginger were analyzed using a population pharmacokinetic-pharmacodynamic modeling approach. The ratio of S-warfarin apparent clearance (CL/F) compared to control was 1.39 +/- 0.06 and 1.14 +/- 0.04 after St John's wort and Asian ginseng pretreatment, respectively. Other pharmacokinetic and pharmacodynamic parameters were unaffected. Coadministration of St John's wort significantly increased S-warfarin CL/F, whereas treatment with Asian ginseng produced only a moderate increase in CL/F. Ginkgo and ginger did not affect the pharmacokinetics of warfarin in healthy subjects. None of the herbs studied had a direct effect on warfarin pharmacodynamics. Studies in anticoagulated patients are warranted to assess the clinical significance of these herb-drug interactions.

Adult↗