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PubMed2006

Relationship between excretion clearance of rhodamine 123 and P-glycoprotein (Pgp) expression induced by representative Pgp inducers.

P-Glycoprotein (Pgp) locates in several tissues in the living body and acts as an efflux pump for many drugs. In this study, the usefulness of intravenous rhodamine 123 (Rho123) administration as a marker for detecting the inducing effect of Pgp by drugs was identified, and the relationship between excretion clearances of Rho123 via Pgp and its expression during treatment with the representative Pgp inducers rifampicin (RFP), dexamethasone (DEX) and St. John's Wort (SJW) were examined in rat liver, intestine and kidney. After pretreatment with RFP (10 mg/kg/d) for 4 d, DEX (50 mg/kg/d) for 4 d or SJW (15 mg/kg/d) for 7 d orally, the biliary excretion of Rho123 after intravenous administration (0.2 mg/kg) increased significantly by 40%, 55% and 14%, respectively, and the intestinal excretion increased significantly by 24%, 50% and 27%, respectively, as compared with the controls. In contrast, there were no notable changes in the urinary excretion of Rho123 among rats that received these inducers. Western blot analysis with a monoclonal antibody for Pgp (C219) showed that Pgp levels in the small intestine and liver in the inducer-treated rats increased markedly as compared with the controls. In addition, there was a significant correlation between the induction levels of Pgp in the liver or small intestine and their clearance ratios (r2=0.7583, p<0.05), but not in the kidney. These observations suggest that the excretion clearances of Rho123 from blood circulation to the small intestine or to the bile after its intravenous administration are useful indicators to assess the Pgp function in the presence of Pgp inducers.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2000

[Consultation and survey for drug interaction in outpatients taking the medicines potentially interact with St. John's Wort].

Ministry Health Welfare of Japan announced the caution for drug interaction of St. John's Wort (SJW), a herbal supplement occasionally used for depression, on May, 2000. Immediately after the announcement, we conducted drug consultation for outpatients prescribed the medicines potentially interacting with SJW. We provided information concerning possible drug interaction with SJW for 741 outpatients (except for pediatrics) during the period of May 22-June 16, 2000. The potential drugs prescribed frequently were warfarin (28.0%), theophylline (19.7%), digitalis (18.4%), carbamazepine (7.2%), disopyramide (6.9%) and cyclosporin (6.3%). Of the patients, 401 subjects were surveyed by collecting the questionnaires to clarify the background of SJW drug interaction. Twenty-two subjects (5.5%) have known commercially available SJW products, 5 subjects (1.2%) have ever taken SJW products before and 2 subjects (0.5%) have taken SJW products concomitant with prescribed medicines. Gender difference was observed in paying attention to SJW products; female subjects (8.6%) tended to have more interest in SJW products than male subjects (2.8%). Two subjects taking SJW have realized for the first time that the supplements they took were SJW products when their package photographs were shown at the consultation. Showing the package photographs might be helpful for making the patients easy to identify the SJW products, because most patients do not pay attention to whether the supplements contain SJW or not. It is recommended that drug consultation should be provided to avoid serious drug interaction with SJW while the outpatients are taking potential medicines prescribed.

Adult↗
PubMed2001

St John's wort for depression: what's the evidence?

There is a moderate amount of evidence to suggest that St John's wort is better than placebo in the short-term management of mild to moderate depressive illness, but there is increasing concern over reports of drug interactions. This article examines the scientific evidence and discusses relevant clinical issues.

Depression↗
PubMed2000

Drug interaction between St. John's wort and cyclosporine.

OBJECTIVE: To report a probable drug interaction between the herbal dietary supplement St. John's wort and cyclosporine. CASE REPORT: A 29-year-old white woman who received a cadaveric kidney and pancreas transplant, with stable organ function and stable cyclosporine concentrations began self-medicating with St. John's wort. After taking St. John's wort supplements for four to eight weeks, her cyclosporine concentrations became subtherapeutic; this was associated with organ rejection. Four weeks after stopping St. John's wort, her cyclosporine concentrations again became therapeutic. Subsequent to this rejection episode, she has developed chronic rejection and now has returned to dialysis. DISCUSSION: St. John's wort is suspected to be a significant inducer of CYP3A4 isoenzyme activity and of P-glycoprotein (P-gp) expression, both of which are important in the metabolism and absorption of cyclosporine. Cyclosporine exhibits a relatively small therapeutic window and is sensitive to medications that can modulate the CYP3A4 isoenzyme and P-gp in both the liver and small intestines. CONCLUSIONS: Patients taking St. John's wort concomitant with other prescription medications whose absorption and metabolism are mediated by the CYP3A4 isoenzyme and P-gp require close monitoring. Patient medication histories should include inquiries into the use of herbal dietary supplements.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2004

Predicting pharmacokinetic herb-drug interactions.

In vitro and in vivo studies have indicated that the induction or inhibition of cytochrome P450 (CYP) is one of the major mechanisms for some clinically important pharmacokinetic herb-drug interactions. Thus, an attempt was made to predict pharmacokinetic herb-drug interactions using the pharmacokinetic principles that are used for predicting drug-drug interactions. The expected AUC ratio was mainly dependent on unbound herbal inhibitor concentration ([I]) and inhibition constant (Ki), hepatic fraction (fh), number of inhibitory herbal constituents (n) and metabolic pathway fraction in hepatic metabolism (fm). Herb-drug interactions would be with low risk if sigma(i=1)n [[Ii]/Ki(i)] is less than 0.1, medium risk if it is between 0.1 and 1.0, and high risk if it is greater than 1. For high clearance drugs, the change of fh x fm had minor influence on AUC ratio when sigma(i=1)n [[Ii]/Ki(i)] values were fixed. Similarly, fm did not affect the AUC ratio for low clearance drugs. It appeared likely to predict a herb-drug metabolic interaction when [I], Ki, fh, fm and n could be determined. However, many herb- and drug-related factors may cause difficulties with the prediction, and well-designed human studies are always necessary.

Area Under Curve↗
PubMed2005

The safety of antidepressant use in pregnancy.

Depression during pregnancy affects an estimated 10 - 20% of women, some of whom will require treatment with antidepressants. It is of great importance that the safety of this particular class of drugs is reviewed, to ensure the optimal treatment of the mother while protecting her unborn child. In this review, current safety data on all available antidepressants are discussed in detail, including the pharmacokinetics of the maternal-fetal unit and the epidemiological studies that have been published to date. The classes of antidepressants discussed include: tricyclics, selective serotonin re-uptake inhibitors and other antidepressants. After reviewing these studies, it is evident that these drugs appear to be relatively safe to take during pregnancy. This evidence-based information will be helpful to women and their healthcare providers, when the decision of whether or not to treat with anti-depressants during pregnancy must be made.

Abortion, Induced↗
PubMed2000

Photooxidation of lens alpha-crystallin by hypericin (active ingredient in St. John's Wort).

Hypericin is the active ingredient in the over the counter antidepressant medication St. John's Wort. Hypericin produces singlet oxygen and other excited state intermediates that indicate it should be a very efficient phototoxic agent in the eye. Furthermore it absorbs in the UV and visible range, which means it can potentially damage both the lens and the retina. Lens alpha-crystallin, isolated from calf lenses, was irradiated in the presence of hypericin (5 x 10(-5) M, 10 mM ammonium bicarbonate, pH 7.0) and in the presence and absence of light (> 300 nm, 24 mW/cm2). Hypericin-induced photosensitized photopolymerization as assessed by sodium dodecylsulfate-polyacrylamide gel electrophoresis. Further analysis of the oxidative changes occurring in alpha-crystallin using mass spectrometry showed specific oxidation of methionine, tryptophan and histidine residues, which increased with irradiation time. Hypericin did not damage the lens protein in the dark. Damage to alpha-crystallin could undermine the integrity of the lens directly by protein denaturation and indirectly by disturbing chaperone function. Therefore, in the presence of light, hypericin can induce changes in lens protein that could lead to the formation of cataracts. Appropriate precautions should be taken to protect the eye from intense sunlight while on this antidepressant medication.

Animals↗
PubMedDate not supplied

Phototoxicity in human lens epithelial cells promoted by St. John's Wort.

St. John's Wort (SJW), an over-the-counter antidepressant, contains hypericin, which absorbs light in the UV and visible ranges and is phototoxic to skin. To determine if it also could be phototoxic to the eye, we exposed human lens epithelial cells to 0.1-10 microM hypericin and irradiated them with 4 J/cm2 UV-A or 0.9 J/cm2 visible light. Neither hypericin exposure alone nor light exposure alone reduced cell viability. In contrast, cells exposed to hypericin in combination with UV-A or visible light underwent necrosis and apoptosis. The ocular antioxidants lutein and N-acetyl cysteine did not prevent damage. Thus, ingested SJW is potentially phototoxic to the eye and could contribute to early cataractogenesis. Precautions should be taken to protect the eye from intense sunlight while taking SJW.

Anthracenes↗
PubMed2000

Consumer use of St. John's wort: a survey on effectiveness, safety, and tolerability.

Despite its poorly described pharmacology, effectiveness, and safety, use of St. John's wort (SJW) is largely unsupervised and unexplored, and can potentially lead to adverse outcomes. We conducted a telephone survey of 43 subjects who had taken SJW to assess demographics, psychiatric and medical conditions, dosage, duration of use, reason for use, side effects, concomitant drugs, professional consultation, effectiveness, relapse, and withdrawal effects. Most subjects reported taking SJW for depression, and 74% did not seek medical advice. Mean dosage was 475.6+/-360 mg/day (range 300-1200 mg/day) and mean duration of therapy was 7.3+/-10.1 weeks (range 1 day-5 yrs). Among 36 (84%) reporting improvement, 18 (50%) had a psychiatric diagnosis. Twenty (47%) reported side effects, resulting in discontinuation in five (12%) and one emergency room visit. Two consumers experienced symptoms of serotonin syndrome and three reported food-drug interactions. Thirteen consumers experienced withdrawal symptoms and two had a depressive relapse. These data suggest the need for greater consumer and provider awareness of the potential risks of SJW in self-care of depression and related syndromes.

Adult↗
PubMed2001

Evaluation of the association between St. John's wort and elevated thyroid-stimulating hormone.

STUDY OBJECTIVE: To evaluate whether St. John's wort is associated with an elevation in thyroid-stimulating hormone (TSH) levels. DESIGN: Retrospective case-control study SETTING: Hamilton, Ontario; September 1998-May 1999. SUBJECTS: Thirty-seven subjects with elevated TSH levels and 37 age- (+/- 6 yrs) and gender-matched subjects with normal TSH levels who resided in the same region. MEASUREMENTS AND MAIN RESULTS: Exposure to St. John's wort during the 3-6 months before TSH measurement was assessed through a telephone interview. A total of 4 of 37 subjects with elevated TSH levels and 2 of 37 subjects with normal TSH levels had taken St. John's wort in that time period. The odds ratio for elevated TSH levels associated with taking St. John's wort was 2.12 (95% confidence interval [CI] 0.36-12.36). CONCLUSION: This study suggests a probable association between St. John's wort and elevated TSH levels. However, because of the wide CIs surrounding the point estimate (which crosses unity), further investigation, including a large, prospective cohort study, is warranted.

Adolescent↗
PubMed2003

Clinic at the health food store? Employee recommendations and product analysis.

STUDY OBJECTIVES: To determine what products health food store employees recommend for depression, to analyze the content of these products based on label claims, and to evaluate employee statements or recommendations for accuracy and safety. METHODS: Twelve health food stores were selected for the study. One investigator approached an employee in each store and asked what they recommended for depression plus five additional questions regarding product use. Thirteen products containing St. John's wort were purchased and analyzed for hypericin and pseudohypericin content using high-performance liquid chromatography (HPLC). Total hypericin content was calculated by adding the values for hypericin and pseudohypericin. RESULTS: All 12 health food store employees recommended a St. John's wort supplement for treatment of depression. Furthermore, numerous comments made by employees regarding St. John's wort and the treatment of depression were unsafe and inaccurate. The HPLC analysis revealed that no product contained +/- 10% of the stated label claim for hypericin content, and two products contained 0% hypericin. The total hypericin content (hypericin plus pseudohypericin) of only two products was within +/- 10% of the label claim for hypericin. CONCLUSIONS: Health food store employees offer health care advice regarding treatment of depression with dietary supplements without proper scientific and medical training. Their comments could cause significant harm to customers. In addition, the inconsistencies of dietary supplement content continue to raise concern for individuals who use these agents as medical treatment.

Anthracenes↗
PubMed2003

A survey of herbal use in children with attention-deficit-hyperactivity disorder or depression.

OBJECTIVE: To examine whether herbal medicines were given to children or adolescents receiving care for attention-deficit-hyperactivity disorder or depression. METHODS: Between October 2000 and July 2001, a 23-item questionnaire was administered in five community mental health centers in Texas. Parents or primary caregivers of children who received a psychiatric assessment were sought for participation. One hundred seventeen caregivers completed a questionnaire. The main outcome measure was primary caregivers' self-report of the use of herbal therapy in their children. RESULTS: The lifetime prevalence of herbal therapy in patients was 20% (23 patients). Eighteen patients (15%) had taken herbal medicines during the past year. Recommendations from a friend or relative resulted in the administration of herbal medicines by 61% of 23 caregivers. Herbal medicines were given most frequently for a behavioral condition, with ginkgo biloba, echinacea, and St. John's wort most prevalent. Almost 83% of caregivers gave herbal medicines alone, whereas 13% gave herbal medicines with prescription drugs. Most caregivers (78%) supervised the administration of herbal therapy in their children; the children's psychiatrists (70%), pediatricians (56%), or pharmacists (74%) typically were not aware of the use. CONCLUSIONS: Most caregivers supervised herbal therapy in their children, without communication with a health professional. A need exists for better communication between health professionals and caregivers regarding the use of herbal therapy.

Adolescent↗