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At least 955 records · Page 53Linked to original sources
PubMed2005

Opposite effects of short-term and long-term St John's wort intake on voriconazole pharmacokinetics.

OBJECTIVES: Constituents of St John's wort (SJW) in vivo induce the cytochrome P450 (CYP) isozymes 3A4, 2C9, and 2C19 but in vitro were shown to inhibit them. This study investigates both short- and long-term effects of SJW on the antifungal voriconazole, which is metabolized by these enzymes. METHODS: In a controlled, open-label study, single oral doses of 400 mg voriconazole were administered to 16 healthy men stratified for CYP2C19 genotype before and on day 1 and day 15 of concomitant SJW intake (300 mg LI 160 3 times daily). Plasma and urine concentrations of voriconazole were determined by liquid chromatography with mass-spectrometric detection. RESULTS: During the initial 10 hours of the first day of SJW administration, the area under the voriconazole plasma concentration-time curve was increased by 22% compared with control (15.5 +/- 6.84 h . microg/mL versus 12.7 +/- 4.16 h . microg/mL, P = .02). After 15 days of SJW intake, the area under the plasma concentration-time curve from hour 0 to infinity was reduced by 59% compared with control (9.63 +/- 6.03 h . microg/mL versus 23.5 +/- 15.6 h . microg/mL, P = .0004), with a corresponding increase in oral voriconazole clearance (CL/F) from 390 +/- 192 to 952 +/- 524 mL/min (P = .0004). The baseline CL/F of voriconazole and the absolute increase in CL/F were smaller in carriers of 1 or 2 deficient CYP2C19*2 alleles compared with wild-type individuals (P < .03). CONCLUSIONS: Coadministration of SJW leads to a short-term but clinically irrelevant increase followed by a prolonged extensive reduction in voriconazole exposure. SJW might put CYP2C19 wild-type individuals at highest risk for potential voriconazole treatment failure.

Administration, Oral↗
PubMed2005

Interaction of St. John's Wort with oral contraceptives: effects on the pharmacokinetics of norethindrone and ethinyl estradiol, ovarian activity and breakthrough bleeding.

OBJECTIVES: This study evaluated the effect of the herbal remedy St. John's Wort on oral contraceptive (OC) therapy with respect to the pharmacokinetics of norethindrone and ethinyl estradiol, ovarian activity and breakthrough bleeding. METHODS: Sixteen healthy women were treated with a low-dose OC (Loestrin 1/20) and a placebo for two consecutive 28-day cycles in a single-blind sequential trial. Treatment with St John's Wort 300 mg three times daily was then added for two additional 28-day cycles. Outcomes compared between control and treatment cycles included the pharmacokinetics of norethindrone and ethinyl estradiol, daily bleeding diaries, follicle growth, changes in cervical mucus and progesterone levels drawn at 7- to 10-day intervals. RESULTS: Treatment with St. John's Wort was associated with a significant 13-15% reduction in the dose exposure from the contraceptive. Breakthrough bleeding increased in the treatment cycles, as did evidence of follicle growth and probable ovulation. CONCLUSION: St. John's Wort is associated with increased metabolism of norethindrone and ethinyl estradiol, breakthrough bleeding, follicle growth and ovulation. Women using OCs should be cautioned that St. John's Wort might interfere with contraceptive effectiveness.

Adult↗
PubMed2006

Does St. John's wort interfere with the antiandrogenic effect of oral contraceptive pills?

BACKGROUND: St. John's wort (SJW), a commonly used herbal remedy, has been shown to compromise the efficacy of drugs, including oral contraceptive pills (OCPs), by inducing cytochrome P-450. We investigated whether the simultaneous use of SJW with OCPs resulted in elevated serum androgen levels with implications of impaired OCP treatment of hirsutism and acne. MATERIALS AND METHODS: Fifteen healthy women were treated with the low-dose OC Loestrin 1/20trade mark for 2 months and then additionally with SJW for 2 months. Androgen and sex hormone-binding globulin (SHBG) levels were measured in serum by immunoassay methods; free testosterone (fT) was calculated. Results were analyzed using the Wilcoxon signed-rank test. RESULTS: There were no statistically significant differences in androgen levels after the addition of SJW in women using Loestrin 1/20trade mark. However, there were decreases in total testosterone and fT levels (10.7% and 15.8%, respectively) along with a small increase in SHBG levels (7.0%). CONCLUSIONS: In women using OCPs and SJW simultaneously, it appears that SJW does not interfere with the antiandrogenic properties of OCPs.

Acne Vulgaris↗
PubMed2006

A Phase II study of St. John's Wort for smoking cessation.

OBJECTIVES: To examine the feasibility and efficacy of St. John's Wort (SJW) for smoking cessation. DESIGN: This one-arm Phase II study utilized an exact two-stage group sequential design with a 1-week run-in period between the start of SJW treatment and the designated quit date. A total of 37 smokers (ages 18-65 years, smoking > or = 10 cigarettes/day) were started on SJW. Thirteen failed to make a verified quit attempt on the predesignated date and were taken off study resulting in 24 evaluable subjects. SETTING: Smokers completed clinic visits at a cancer center with interval telephone calls and mailings. INTERVENTION: Standardized SJW, 450 mg capsules taken orally twice daily along with cessation counseling messages. MAIN OUTCOME MEASURES: Subjects completed validated surveys and a focused physical examination at baseline. Evaluable subjects were defined as those subjects who made a confirmed quit attempt on their "quit date" 1 week following initiation of SJW. Smoking status was determined through self-report and bioverification using carbon monoxide (CO) testing. RESULTS: Among evaluable subjects, the 12-week quit rate was 37.5% (9/24). Quitters had no significant change in weight from baseline to 12-weeks cessation. Use of SJW was generally well tolerated. CONCLUSIONS: Based upon these results (which suggest that SJW may be effective in maintaining smoking cessation) and the high compliance and few AEs, we conclude that SJW demonstrates feasibility for use in smoking cessation. If SJW proves to be effective in larger controlled studies, it could represent a less expensive, more readily accessible and well-tolerated agent to promote tobacco cessation.

Adolescent↗
PubMed2006

Health-related quality of life and its predictive role for analgesic effect in patients with painful polyneuropathy.

Painful polyneuropathy is a common neuropathic pain condition. The present study describes health-related quality of life (HRQL) in a sample of patients with painful polyneuropathy of different origin and the possible predictive role of HRQL for analgesic effect. Ninety-three patients with a diagnosis of painful polyneuropathy were included in the analysis. Data were obtained from three randomised, placebo-controlled cross-over studies testing the effect of different drugs on polyneuropathic pain (St. John's wort, venlafaxine/imipramine and valproic acid). Patients completed a HRQL questionnaire (SF-36) after a drug-free baseline period and at the end of each treatment period. At baseline, all eight SF-36 scores were lower than in the normal population. No significant differences were found between SF-36 scales during placebo and treatment with valproic acid and St. John's wort. Those two drugs had not shown a pain relieving effect in former analysis. The SF-36 scale of bodily pain (BP) was improved by venlafaxine treatment (p=0.023). General health (GH) and vitality (VT) were improved under treatment with imipramine (GH: p=0.006, VT: p=0.015). In a multivariate logistic regression analysis, baseline SF-36 scores predicted subsequent response to pharmacological treatment. Results show an impaired HRQL in painful polyneuropathy and suggest that HRQL may predict response to analgesic treatment.

Adult↗
PubMed2006

Herbal supplements: Facts and myths--talking to your patients about herbal supplements.

The use of herbal supplements in the United States is steadily growing and raises concerns about safety, efficacy, and how they affect safe patient care. The direct health risks associated with herbal supplements include hypertension, prolonged bleeding, and the potential for drug-herb interactions. These potential drug interactions are of particular concern for patients undergoing anesthesia. This article provides a review of literature on the 10 most popular herbal supplements and addresses the herbal supplements' reported use, possible adverse effect(s), patient teaching, possible drug interaction(s), and recommendations regarding discontinuation before surgery.

Androgen Antagonists↗
PubMed2004

Extracts of St. John's wort and various constituents affect beta-adrenergic binding in rat frontal cortex.

The present study was designed to get further insight into the mode of antidepressant action of extracts prepared from St. John's wort (SJW) and relevant active constituents. Down-regulation of central beta-adrenergic receptors (beta-AR's) has been widely considered a common biochemical marker of antidepressant efficacy. Although previous studies have reported a beta-AR down-regulation for SJW extracts, in vivo studies that compare the effects of SJW extracts with those of relevant active constituents on beta-AR density have not been done yet. We used quantitative radioligand receptor-binding-studies to examine in rats the effects of short-term (2 wks) and long-term (8 wks) administration of different SJW extracts and constituents on beta-AR binding in rat frontal cortex. The effects were compared to those of the standard antidepressants imipramine and fluoxetine. [125I]CYP binding to beta-AR was found to be decreased after short as well as after long-term treatment with imipramine (36%, 40%). Short-term treatment with fluoxetine decreased the number of beta-adrenergic receptors (17%) while long-term treatment with fluoxetine elicited an increase (14%) in beta-AR-binding. This effect was comparable to that of the lipophilic CO2 extract which decreased beta-AR-binding (13%) after two weeks and slightly increased the number of beta-AR's after 8 weeks (9%). Short-term treatment with the methanolic SJW extract decreased beta-AR-binding (14%), no effects for this extract were observed after 8 weeks. Treatment with hypericin led to a significant down-regulation (13%) of beta-AR's in the frontal cortex after 8-weeks, but not after 2 weeks, while hyperforin (used as trimethoxybenzoate, TMB), and hyperoside were ineffective in both treatment paradigms. Compared to the SJW extracts and single compounds the effect of imipramine on beta-AR-binding was more pronounced in both treatment paradigms.

Animals↗
PubMed2006

Hyperforin: more than an antidepressant bioactive compound?

Hyperforin is a lipophilic compound that is present in great amounts in St. John's wort and that has been described as the main responsible for the antidepressant effects of this medicinal plant. In the last few years, evidence has accumulated pointing to other different effects of hyperforin with potential pharmacological interest. They include other neurological effects, effects on inflammation, as well as antibacterial, antitumoral and antiangiogenic effects.

Angiogenesis Inhibitors↗
PubMed2005

Toxicity and drug interactions associated with herbal products: ephedra and St. John's Wort.

Health care providers are being increasingly confronted with the use of herbal medications by their patients. It is imperative that patients be questioned regarding herbal preparation use and that health care providers become familiar with these agents. Research into the active components and mechanisms of action of various herbals is ongoing [350]. Long-range studies need to be performed to follow patients for efficacy or toxicity in chronic use [351,352]. Adverse reactions to herbal remedies should be reported to the FDA MedWatch at http://www.fda.gov/medwatch. As withany therapeutic agent, risk of use must always be weighed against potential benefits.

Ephedra↗
PubMed2004

Hyperforin modifies neuronal membrane properties in vivo.

Hyperforin, the major active constituent of St. John Wort (SJW) extract, affects several neurotransmitter systems in the brain putatively by modulation of the physical state of neuronal membranes. Accordingly, we tested the effects of SJW extract and of hyperforin on the properties of murine brain membrane fluidity. Oral administration of SJW extract and of hyperforin sodium salt results in significant hyperforin brain levels. Treatment of mice with hyperforin leads to decreased annular- and bulk fluidity and increased acyl-chain flexibility of brain membranes. All hyperforin related changes of membrane properties were significantly correlated with the corresponding hyperforin brain levels. Our data emphasises a membrane interaction of hyperforin that possibly contributes to its pharmacological effects.

Administration, Oral↗
PubMed2005

Photoinduced antitumour effect of hypericin can be enhanced by fractionated dosing.

The in vivo antitumour activity of the natural photosensitizer hypericin was evaluated. C3H/DiSn mice were inoculated with fibrosarcoma G5:1:13 cells. When the tumour reached a volume of 40-80mm3 the mice were intraperitoneally injected with hypericin, either in a single dose (5mg/kg; 1 or 6h before laser irradiation) or two fractionated doses (2.5 mg/kg; 6 and 1 h before irradiation with laser light; 532 nm, 70mW/cm2, 168 J/cm2). All tumours in control groups treated with hypericin alone as well as those irradiated with laser light alone had similar growth rates and none of these tumours regressed spontaneously. Complete remission of tumour in photodynamic therapy (PDT)-treated groups was similar (14-17% single dose vs. 33% fractionated dose), but the fractionated schedule of hypericin dosing was found to be more efficient than the single dose, measured by survival assay (p < 0.05). Our experimental model showed that fractionated administration of hypericin can produce a better therapeutic response than single administration.

Animals↗
PubMed2005

Safety of St. John's Wort extract compared to synthetic antidepressants.

The clinical efficacy of some standardized St. John's Wort extracts (SWEs) such as WS((R)) 5570, WS((R)) 5572 or LI 160 in the treatment of mild, moderate and severe major depression has been demonstrated in 38 controlled clinical trials and two recent meta-analyses. Sixteen post-marketing surveillance studies with such preparations, based on a total of 34,804 patients, recorded an incidence of adverse events (AEs) among patients between 0% and 6%. Of these studies, the four large-scale surveillance studies with a total of 14,245 patients recorded a rate of AEs ranging from 0.1% to 2.4% and a drop-out rate due to AEs of 0.1-0.9%. This is at least ten-fold lower than that recorded with synthetic antidepressants. AEs associated with SWE treatment were mild and transient in nearly all cases. As with synthetic antidepressants, pharmacokinetic interactions may occur occasionally as a result of activity changes of drug-metabolising and drug-transporting proteins, especially CYP 3A4 and P-gp. Risks to the patient are not caused by SWE but by drugs with a narrow therapeutic range. Consequently, SWE preparations should not be taken concurrently with other antidepressants, with coumarin-type anticoagulants, the immunosuppressants cyclosporine and tacrolimus, protease and reverse transcriptase inhibitors used in anti-HIV treatment or with certain antineoplastic agents. However, such cases are extremely rare and, with medical supervision, easily avoided. In conclusion, the safety of SWE must be considered more favourable than that of synthetic antidepressants.

Antidepressive Agents↗
PubMed2006

Histomorphological changes in murine fibrosarcoma after hypericin-based photodynamic therapy.

Histomorphological changes in murine fibrosarcoma after photodynamic therapy (PDT) based on the natural photosensitizer hypericin were evaluated. C3H/DiSn mice were inoculated with fibrosarcoma G5:1:13 cells. When the tumour reached a volume of 40-80 mm(3) the mice were intraperitoneally injected with hypericin, either in a single dose (5 mg/kg; 1 or 6 h before laser irradiation) or two fractionated doses (2.5 mg/kg; 6 and 1 h before irradiation with laser light; 532 nm, 70 mW/cm(2), 168 J/cm(2)). All groups of PDT-treated animals with single and fractionated hypericin dosing presented primary vascular reactions including vascular dilatation, congestion, thrombosis and oedema. Two hours after PDT there were necrotic changes with small, rather focal appearance. One day after therapy the necrotic areas were enhanced, often affecting a complete superficial layer of tumour tissue. Necrotic areas were accompanied with inflammation and haemorrhages.

Animals↗
PubMed2006

Hyperforin and its analogues inhibit CYP3A4 enzyme activity.

Literature indicates that herb-drug interaction of St. John's wort is largely due to increased metabolism of the co-administered drugs that are the substrates of cytochrome P450 (CYP) 3A4 enzyme, alteration of the activity and/or expression of the enzyme. The major St. John's wort constituents, acylphloroglucinols, were evaluated for their effects on CYP3A4 enzyme activity to investigate their roles in herb-drug interaction. Hyperforin and four oxidized analogues were isolated from the plant and fully characterized by mass spectral and NMR analysis. These acylphloroglucinols inhibited activity of CYP3A4 enzyme potently in the fluorometric assay using the recombinant enzyme. Furoadhyperforin (IC(50) 0.072 microM) was found to be the most potent inhibitor of CYP3A4 enzyme activity, followed by furohyperforin isomer 1 (IC(50) 0.079 microM), furohyperforin isomer 2 (IC(50) 0.23 microM), hyperforin (IC(50) 0.63 microM) and furohyperforin (IC(50) 1.3 microM). As the acylphloroglucinols are potent inhibitors of the CYP3A4 enzyme, their modulation of the enzyme activity is unlikely to be involved in increased drug metabolism by St. John's wort.

Bridged Bicyclo Compounds↗
PubMed2005

Temperature stress can alter the photosynthetic efficiency and secondary metabolite concentrations in St. John's wort.

Temperature stress is known to cause many physiological, biochemical and molecular changes in plant metabolism and possibly alter the secondary metabolite production in plants. The hypothesis of the current study was that temperature stress can increase the secondary metabolite concentrations in St. John's wort. Plants were grown under controlled environments with artificial light using cool white fluorescent lamps and CO2 enrichment and 70-day-old plants were subjected for 15 days to different temperature treatments of 15, 20, 25, 30 and 35 degrees C before harvested. Major aim of the study was to increase the major secondary metabolites in St. John's wort by applying temperature stress and to evaluate the physiological status of the plant especially the photosynthetic efficiency and peroxidase activity of the leaf tissues exposed to different temperatures under precisely controlled environmental factors. Results revealed that relatively high (35 degrees C) or low (15 degrees C) temperatures reduced the photosynthetic efficiency of the leaves of St. John's wort plants and resulted in low CO2 assimilation. Net photosynthetic rates and the maximal quantum efficiency of PSII photochemistry of the dark adopted leaves (phi(p)max) decreased significantly in the leaves of plants grown under 35 or 15 degrees C temperature treatments. High temperature (35 degrees C) treatment increased the leaf total peroxidase activity and also increased the hypericin, pseudohypericin and hyperforin concentrations in the shoot tissues. These results provide the first indication that temperature is an important environmental factor to optimize the secondary metabolite production in St. John's wort and controlled environment technology can allow the precise application of such specific stresses.

Hypericum↗