Contributions of hepatic and intestinal metabolism and P‐glycoprotein to cyclosporine and tacrolimus oral drug delivery.  |  Tacrolimus (TAC) is a macrolide immunosuppressant frequently used after kidney, liver and heart transplantations. 2020 Jun 30;9(6):2638-2649. doi: 10.4103/jfmpc.jfmpc_1094_19. However, conflicting data regarding its benefits and risks exist, and the last large meta-analysis on St John's wort use for depression was done in 2008, with no updated meta-analysis available. St John’s wort (Hypericum perforatum) has been known for centuries for its therapeutic properties and its efficacy as an antidepressant has been confirmed by a growing body of evidence. 2003 Jun;253(3):140-8. doi: 10.1007/s00406-003-0417-6. Please enable it to take advantage of the complete set of features! eCollection 2018. Menopause. Oxford University Press is a department of the University of Oxford. St. John’s wort is the common name for Hypericum perforatum , a yellow flower with a long and rich history. Yonsei Med J. St John’s wort may also impact on the breakdown of other drugs by She was given three doses of intravenous pethidine followed by regular paracetamol and tramadol for pain from a broken leg. Renal function remained stable during SJW treatment as indicated by creatinine and urea concentrations (Table 1). Design : Systematic review and meta-analysis of trials revealed by searches. Detailed patient characteristics are reported in Table 1. There are no graphs or illustrations present in the article. St. John's Wort for Mild and Moderate Depression Outperforms Placebo and Is Comparable to Antidepressants, but the Evidence Has Limitations. To address whether St John's wort is useful for the treatment of depression we attempted to retrieve all English-language articles with data on the efficacy, safety, and availability of St John's wort. It has been postulated that the hypericin component in St John's wort is a hepatic metabolic enzyme CYP1A2 inducer while the hyperforin component is a CYP3A4 inducer (Markowitz et al., 2003). Thank you for submitting a comment on this article. St John’s wort decreased the plasma concentration of the active metabolite SN-38 in cancer patients receiving irinotecan treatment. When the patient was quizzed regarding her recent use of medicines, illicit drug u… Patients were included if the creatinine clearance was >30 ml/min. Breidenbach T, Hoffmann MW, Becker T, Schlitt H, Klempnauer J. Ingrid Mai, Elke Störmer, Steffen Bauer, Hagen Krüger, Klemens Budde, Ivar Roots, Impact of St John's wort treatment on the pharmacokinetics of tacrolimus and mycophenolic acid in renal transplant patients, Nephrology Dialysis Transplantation, Volume 18, Issue 4, April 2003, Pages 819–822, https://doi.org/10.1093/ndt/gfg002. MPA pharmacokinetics remained unaffected by comedication with hypericum extract. Acute transplant rejections due to decreased cyclosporine concentrations with co‐administration of SJW have been reported in several cases [6,7]. St John’s wort did not alter the pharmacokinetics of tolbutamide, but increased the incidence of hypoglycaemia. Compartment free pharmacokinetic analysis was conducted using WinNonLin Pro 1.5 (Pharsight Corp., Mountain View, CA, USA) to determine AUC(0–12), Cmax, tmax and Ctrough. Comediations were kept unchanged throughout the study. Perloff MD, von Moltke LL, Störmer E, Shader RI, Greenblatt DJ. The study was approved by the ethical committee of the Humboldt University of Berlin, and all patients consented in writing to their participation in this study. Get the latest public health information from CDC: https://www.coronavirus.gov, Get the latest research information from NIH: https://www.nih.gov/coronavirus, Find NCBI SARS-CoV-2 literature, sequence, and clinical content: https://www.ncbi.nlm.nih.gov/sars-cov-2/. Trough levels of TAC were determined regularly throughout the study and dosage adjustments were made to keep TAC trough concentrations in the therapeutic range of 5–15 ng/ml. Two weeks after discontinuation of SJW, TAC doses were reduced to a median of 6.5 mg/day. Moore LB, Goodwin B, Jones SA et al. St. John's Wort. Immune checkpoint inhibitor–associated hypercalcaemia, Receive exclusive offers and updates from Oxford Academic, Furosemide, cerivastatin, methylprednisolon, benazepril, Methylprednisolon, metoprolol, benzbromaron, Torasemide, metoprolol, nitrendipin, benzbromaron, Methylprednisolon, benazepril, moxonidine, metoprolol, Furosemide, methylprednisolon, perindoprile, metoprolol, Copyright © 2021 European Renal Association - European Dialysis and Transplant Association. Email: ingrid.mai@charite.de. Conclusions. In summary, SJW treatment resulted in a dramatic decrease (>50%) in the bioavailability of TAC. Can the assessment of ultrasound lung water in haemodialysis patients be simplified? Pharmacokinetic parameters of TAC and MPA acid with and without comedication with SJW extract. Conclusions: St John’s wort extracts are effective antidepressants. Lower limits of quantification were 1.5 ng/ml and 0.1 µg/ml for TAC and MPA, respectively. Background. Clipboard, Search History, and several other advanced features are temporarily unavailable. If SJW is still the antidepressant of choice, patients need to be closely monitored and dose adjustments of TAC have to be made accordingly. The mean age of the participants was 50.4 years. The difference in duration of hot flashes between groups was not significant on the 4th week of intervention (P = 0.27); however, it was statistically significant between the two groups on the 8th week of treatment (P < 0.001). It inhibits monoamine oxidase[2][2] SJW extracts contain a variety of different compounds [2], with hypericin, pseudohypericin and hyperforin presumed responsible for the drug's antidepressive activity. Women were treated with St John's wort extract or placebo for 8 weeks. A review of effective herbal medicines in controlling menopausal symptoms. St. John’s wort is not your only option for treating SAD. The search included other aspects of the usage of St John's Wort, such as side-effects, mechanism of action and drug interactions. 2018. Both groups responded to the interventions, and the within-group differences in frequency, duration, and severity of hot flashes were statistically significant (P < 0.05). Certain plants have been found to have molecular components that are identical in structure and function to human hormones. TAC trough levels, corrected for dose, decreased from a median 10.8 ng/ml before SJW administration to 3.8 ng/ml after 2 weeks of combination treatment (Table 2, Figure 2). Johne A, Schmider J, Brockmöller J et al. Administration of SJW extract to patients receiving TAC treatment can result in a serious drug interaction leading to markedly reduced TAC blood concentrations associated with the risk of organ rejection. 2017 Nov 25;9(11):5826-5833. doi: 10.19082/5826. The serotonin syndrome was suspected and so tramadol was withheld and cyproheptadine given. The present study was designed to investigate the effect of St. John's Wort (Hypericum perforatum) in restraint stress-induced behavioral and biochemical alterations in mice. Royal Jelly Supplementation Improves Menopausal Symptoms Such as Backache, Low Back Pain, and Anxiety in Postmenopausal Japanese Women. Background: Saint John’s wort (Hypericum perforatum L., HP) is commonly registered in Europe under the THR scheme (Traditional Herbal Registration) or licensed as a medicine. Nahrstedt A, Butterweck V. Biologically active and other chemical constituents of the herb of Hypericum perforatum L. Johne A, Brockmöller J, Bauer S, Maurer A, Langheinrich M, Roots I. Pharmacokinetic interaction of digoxin with an herbal extract from St John's wort (Hypericum perforatum). Antidepressants are used to manage stress and their related effects. Black cohosh and St. John's wort (GYNO-Plus) for climacteric symptoms. (A) Effect of SJW co‐administration on the blood concentrations of TAC. Statistical significance between the two treatment conditions was assessed using a Wilcoxon‐test (SPSS 10.0, SPSS Inc., Chicago, IL, USA). After the end of the study, TAC doses were adjusted to achieve typical pre‐study trough concentrations for each patient. Presumably, SJW influenced the TAC pharmacokinetics through induction of both mechanisms; however, relative contributions cannot be differentiated in this study. Taken in combination with other drugs, St John’s wort can boost the effect of the other drug, which then increases the risk of negative reactions. Differences were considered statistically significant with P<0.05. The fall-off in frequency of hot flashes on the 4th and 8th weeks of intervention was more evident in women receiving St John's wort, and the differences between groups were statistically significant (P = 0.005 and P < 0.001, respectively). Patients received 600 mg SJW extract (once daily two tablets Jarsin300™, Lichtwer Pharma, Berlin, Germany) for 14 days in addition to their normal regimen of TAC (Prograf™, Fujisawa Healthcare, Inc., Deerfield, IL, USA) and mycophenolate mofetil (CellCept™, Hoffmann‐La Roche AG, Basel, Switzerland). National Center for Biotechnology Information, Unable to load your collection due to an error, Unable to load your delegates due to an error. 2006 Feb;107(2 Pt 1):247-55. doi: 10.1097/01.AOG.0000196504.49378.83. For full access to this pdf, sign in to an existing account, or purchase an annual subscription. 2015 Feb 10;4:65. doi: 10.1186/s40064-015-0808-y. The objectives of this review are to (1) evaluate the efficacy and safety of SJW in adults with MDD compared to placebo and active comparator and (2) evaluate whether the effects vary by severity of MDD. Introduction. Dietary restrictions included caffeine, ethanol, grapefruit juice and smoking. Miller, L. (2001). NIH Objective: Because of a decline in estradiol levels, premenopausal, perimenopausal, and postmenopausal women experience symptoms related to vasomotor instability. Nonetheless unregulated medical products and food supplements are accessible through the internet which are often of poor quality. This study investigated the effect of St John's wort (SJW) extract on the pharmacokinetics of the immunosuppressants tacrolimus (TAC) and mycophenolic acid (MPA). Mycophenolate mofetil is typically combined with TAC or cyclosporine, because of synergistic effects from their different mechanisms of action. Drug interactions known or potentially associated with St. John’s Wort. St John's wort is a popular herbal remedy recommended by Traditional Chinese Medicine (TCM) practitioners and licensed and widely prescribed for depression in many European countries. Dürr D, Stieger B, Kullak‐Ublick GA et al. A systematic review of non-hormonal treatments of vasomotor symptoms in climacteric and cancer patients. St. John’s wort exploded onto the health scene a number of years ago when it was discovered that it could be used as an herbal cure in the treatment of depression.Since then, the herb has fallen from the front pages of the health news. It furthers the University's objective of excellence in research, scholarship, and education by publishing worldwide, This PDF is available to Subscribers Only. A total of 100 women participated in a clinical trial conducted in an academic medical center in Shiraz-Iran. MPA pharmacokinetic parameters were not affected by co‐administration of SJW (Table 2, Figure 1B). Results: Correspondence and offprint requests to: Dr Ingrid Mai, Institut für Klinische Pharmakologie der Charité, Humboldt‐Universität zu Berlin, Schumannstr. MPA plasma concentrations were determined by homogenous enzyme immunoassay (Emit™ using a COBAS MIRA S analyser, Hoffmann‐La Roche AG, Basel, Switzerland). St John's wort for depression - Volume 186 Issue 2 - Klaus Linde, Michael Berner, Matthias Egger, Cynthia Mulrow. St John's wort induces hepatic drug metabolism through activation of the pregnane X receptor. Your comment will be reviewed and published at the journal's discretion. eCollection 2015. Chung DJ, Kim HY, Park KH, Jeong KA, Lee SK, Lee YI, Hur SE, Cho MS, Lee BS, Bai SW, Kim CM, Cho SH, Hwang JY, Park JH. An option for the primary care treatment of depressive patients? Eur Arch Psychiatry Clin Neurosci. Ebrahimi A, Tayebi N, Fatemeh A, Akbarzadeh M. J Family Med Prim Care. An involvement of transmembrane transporters such as P‐gp in the disposition of MPA has not been shown. The fact that induction of CYP3A4 and P‐gp by SJW extract had no effect on the pharmacokinetics of MPA is consistent with a limited contribution of the enzyme and the transporter in MPA biotransformation. When combined with other medications, it can either cause a serious side effect or can interfere with the actions of the other drugs. Asama T, Matsuzaki H, Fukushima S, Tatefuji T, Hashimoto K, Takeda T. Evid Based Complement Alternat Med. Bauer S, Störmer E, Kerb R, Johne A, Brockmöller J, Roots I. F Ruschitzka and colleagues (Feb 12, p 548)1 reported on a drug interaction between St John's wort and ciclosporin. A stressful stimulus is a crucial determinant of health and disease. PUBMED was systematically searched to identify studies describing pharmacokinetic interactions involving St John's wort. Statistical analysis was carried out by using descriptive statistics and multivariate analysis. A Medline search was conducted for the period January 1985 to December 1999. St. John’s Wort (SJW) is a botanical supplement widely used as an over-the-counter treatment of depression and a variety of other conditions associated with anxiety and nerve pain. St John's wort (Hypericum perforatum, SJW) extracts are increasingly used for the treatment of mild to moderate depression [1] and are available without prescription in many countries. Regional anticoagulation with calcium-free dialysate containing citrate in chronic haemodialysis patients, Serum bicarbonate is associated with kidney outcomes in autosomal dominant polycystic kidney disease, Hyponatremia and other electrolyte abnormalities in patients receiving immune checkpoint inhibitors. Roby CA, Anderson GD, Kantor E, Dryer DA, Burstein AH. Hypericum perforatum L. (Hypericaceae) known as St John's wort is one of the most widely used herbal medicines around the world. Individual, dose‐corrected TAC through concentrations before, during, and after SJW treatment. Electron Physician.  |  St John's wort (Hypericum perforatum, SJW) extracts are increasingly used for the treatment of mild to moderate depression [] and are available without prescription in many countries.SJW extracts contain a variety of different compounds [], with hypericin, pseudohypericin and hyperforin presumed responsible for the drug's antidepressive activity. Due to the fact that St. John's wort is not regulated by the Food and Drug Administration (FDA), many questions exist about the safety and efficacy of this product. 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. Hebert MF. The MPA dose was 1000–2000 mg/day and as the therapeutic concentration range is yet undefined, dose changes were allowed if indicated by increased side effects. We conducted this study to compare the efficacy of St John's wort with that of placebo in women with hot flashes.  |  Co‐administration of SJW extract significantly reduced the area under the plasma‐concentration time curve as well as the peak and trough blood concentrations of TAC (Table 2). Two weeks after discontinuation of SJW treatment, trough levels increased again to 7.6 ng/ml and patients returned to their previous dose ∼4 weeks after the end of the study. We searched PubMed, CINAHL, PsycINFO, CENTRAL, Embase, AMED, MANTIS, Web … Considering the current debate about the value of synthetic antidepressants,4 one wonders why they are not used more widely. 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. Methods. Ten renal transplant patients (six male and four female) at least 2 years post‐organ transplantation under stable immunosuppressant treatment with TAC (eight with mycophenolate mofetil comedication) were enrolled in the study. Obstet Gynecol. HHS St. John’s wort is sold as a dietary supplement in the United States, where the standards for selling supplements are less strict than the standards for prescription or over-the-counter drugs. Results. 2009 Mar-Apr;16(2):307-14. doi: 10.1097/gme.0b013e31818572a0. Both, metabolic (cytochrome P‐450) and drug transport (P‐glycoprotein) mechanisms have been discussed as the cause for the SJW drug interaction and in vitro studies suggest that both mechanisms contribute to the observed decrease in bioavailability under SJW [8,9]. eCollection 2020 Jun. Al-Akoum M, Maunsell E, Verreault R, Provencher L, Otis H, Dodin S. Menopause. Alterations in cyclosporin A pharmacokinetics and metabolism with Saint John's wort treatment in renal transplant patients. St. John’s wort has become one of the most popular herbal supplements for the treatment of depression. In order to achieve sufficient immunosuppression, the TAC dose had to be adjusted in all 10 patients, from a median of 4.5 mg/day to 8.0 mg/day. St John's Wort induces intestinal P‐glycoprotein/MDR1 and intestinal and hepatic CYP3A4. The majority of MPA is conjugated to d‐glucuronic acid and excreted in the urine, and only a small amount of the drug is metabolized by CYP enzymes. Investigation of the role of herbal medicine, acupressure, and acupuncture in the menopausal symptoms: An evidence-based systematic review study. 1999 Mar;37(3):111-9. Values represent the mean±SEM of 10 patients. Final TAC and MPA trough levels were measured 2 weeks after discontinuation of SJW treatment. bPatients without mycophenolate mofetil comedication. This site needs JavaScript to work properly. St. John’s wort is a plant with yellow flowers that has been used in traditional European medicine as far back as the ancient Greeks. St John's wort: effect on CYP3A4 activity. eCollection 2017 Nov. Springerplus. It was originally harvested for the feast of St. John the Baptist. TAC blood concentrations were determined by microparticle enzyme immunoassay using an IMX analyser (Abbott Laboratories, Chicago, IL, USA). Drug interaction of St John's wort with cyclosporin. St. John's Wort Regulates Proliferation and Apoptosis in MCF-7 Human Breast Cancer Cells by Inhibiting AMPK/mTOR and Activating the Mitochondrial Pathway. St. John’s wort (Hypericum perforatum), a plant that grows in the wild, has been used for centuries for mental health conditions.It’s widely prescribed for depression in Europe. Objective: All 10 patients complied with the dosage requirements for SJW (determined by measurement of hypericin and pseudohypericin in plasma) and TAC, two patients were without mycophenolate mofetil comedication and were therefore excluded from the MPA data analysis. TAC trough levels are routinely monitored and dose adjustments are made to achieve therapeutic blood concentrations of 5–15 ng/ml. 20/21, D‐10098 Berlin, Germany. Although it is one of the most popular herbal preparations in this country, outselling standard prescription medications for depression, its effectiveness remains in doubt. Median dose‐corrected AUC(0–12) values decreased from a baseline median of 180 ng/h/ml to 75.9 ng/h/ml after 2 weeks of SJW treatment (Figure 1A). The reduced bioavailability for a number of orally dosed drugs that has been observed as a result of comedication with SJW [3–7] can be explained by an induction of drug metabolizing enzymes (CYP3A) and drug transporters (P‐gp) via the PXR receptor, which is caused by certain constituents of SJW extracts [8]. St. John’s wort can weaken how well other drugs work, including antidepressants, birth control pills, cyclosporine (an anti-rejection drug), digoxin (a heart drug), HIV drugs, cancer medications, and blood thinners such as Coumadin. 2018 Mar 23;19(4):966. doi: 10.3390/ijms19040966. Blood concentrations obtained under SJW treatment have been corrected for the TAC dose administered on the day of the kinetic measurements. 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