St John's Wort Supplements Endanger the Success of Organ Transplantation

Ernst, Edzard

doi:10.1001/archsurg.137.3.316

Cited by 106 publications

(29 citation statements)

References 26 publications

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“…In another study, in which intubation techniques were used to deliver cyclosporine to different parts of the gastrointestinal tract in healthy volunteers, there was a significant inverse correlation between cyclosporine absorption and tissue P-glycoprotein mRNA levels at the site of administration [23]. Conversely, induction of both P-glycoprotein and CYP3A4 by rifampicin [24] or plant extracts from St John's Wort [25] caused a clinically relevant decrease in cyclosporine blood levels leading to acute transplant rejection in patients using cyclosporine.…”

Section: Resultsmentioning

confidence: 99%

Induction of Cytochrome P450 3A4 and P-Glycoprotein by the Isoxazolyl- Penicillin Antibiotic Flucloxacillin

Huwyler¹,

Wright²,

Gutmann³

et al. 2006

CDM

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Clinical findings indicate that co-administration of the isoxazolyl-penicillin flucloxacillin with cyclosporine may reduce the plasma concentrations of cyclosporine. We have explored in the present study if induction of cytochrome P450 3A4 or P-glycoprotein may offer a mechanistic explanation of the observed effects. Flucloxacillin is neither an inhibitor nor a substrate of drug metabolizing cytochrome P450 isoenzymes (CYP3A4, 1A2, 2C9, 2C19 and 2D6) or P-glycoprotein as shown by an in vitro assay for CYP inhibition, a fluorescent indicator assay for P-glycoprotein inhibition and a functional P-glycoprotein ATPase assay. However, incubation of human LS 180 colorectal adenocarcinoma cells with flucloxacillin led to a dose-dependent induction of MDR1 as well as of CYP3A4 mRNA, which was also confirmed in primary human hepatocytes. At high concentrations, flucloxacillin activated the human Pregnane-X-Receptor, PXR, a ligand-dependent transcription factor that is the target of many drugs that induce CYP3A4, with consequences for the metabolism of other drugs. Liver microsomes from control rats or rats, which received for 3 consecutive days 100 mg/kg of oral flucloxacillin, were used to study the metabolism and metabolite pattern of midazolam, a model substrate of CYP 3A4. There was a trend towards a higher intrinsic microsomal clearance of midazolam using microsomes from flucloxacillin treated rats. In addition, there was a significant increase in the formation of the principal midazolam metabolites 1-hydroxy midazolam, 4-hydroxy midazolam and 1,4-dihydroxy midazolam as compared to controls. These findings indicate that flucloxacillin has the potential to induce expression of both CYP3A4 as well as P-glycoprotein, most likely through activation of the nuclear hormone receptor PXR. This would offer an explanation for the observed clinical drug-drug interactions between the antibiotic and cyclosporine.

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Section: Resultsmentioning

confidence: 99%

Induction of Cytochrome P450 3A4 and P-Glycoprotein by the Isoxazolyl- Penicillin Antibiotic Flucloxacillin

Huwyler¹,

Wright²,

Gutmann³

et al. 2006

CDM

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“…Reduced drug levels of ethinyl estradiol (10), indinavir (11), and cyclosporine (12,13) have been reported in patients using St. John’s wort. In 1 study of organ transplant patients, St. John’s wort caused a decrease of almost 50% in the concentration of cyclosporine (14).…”

Section: Cardiovascular Adverse Effects Of Herbal Remediesmentioning

confidence: 99%

Use of Herbal Products and Potential Interactions in Patients With Cardiovascular Diseases

Tachjian

Maria

Jahangir

2010

Journal of the American College of Cardiology

351

229

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More than 15 million people in the United States consume herbal remedies or high-dose vitamins. The number of visits to providers of complementary and alternative medicine exceeds those to primary care physicians, for annual out-of-pocket costs of $30 billion. Use of herbal products forms the bulk of treatments, particularly by elderly persons who also consume multiple prescription medications for comorbid conditions, which increases the risk of adverse herb-drug-disease interactions. Despite the paucity of scientific evidence supporting the safety or efficacy of herbal products, their widespread promotion in the popular media and the unsubstantiated health care claims about their efficacy drive consumer demand. In this review, we highlight commonly used herbs and their interactions with cardiovascular drugs. We also discuss health-related issues of herbal products and suggest ways to improve their safety to better protect the public from untoward effects.

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“…St. John's wort, an herbal preparation used as part of an alternative prescription for depression, decreases CNI levels by potent cytochrome P450 induction. Transplant patients should be cautioned against its use, because it has been linked to acute rejection episodes (34).…”

Section: Drug Therapymentioning

confidence: 99%

Management of Cardiovascular Disease in Renal Transplant Recipients

Shirali¹,

Bia²

2008

Clinical Journal of the American Society of Nephrology

110

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Cardiovascular disease is a major cause of graft loss and the leading cause of death in renal transplant recipients. Although there are robust data on the frequency of risk factors and their contributions to cardiovascular disease in this population, few trials have demonstrated the benefit of modifying these risk factors to reduce cardiovascular events. Nevertheless, it is widely accepted that the clinical acumen filtered through the best available studies in the general population be used to treat individual renal transplant recipients given their high cardiovascular mortality. Transplant task forces and the Kidney Disease Outcomes Quality Initiative have created guidelines for this purpose. This review examines the data available for prevention and treatment of major risk factors contributing to cardiovascular disease in renal transplant recipients. The contribution of immunosuppressive agents to each risk factor and the evidence to support lifestyle modification as well as drug therapy are examined. Reducing cardiovascular risk factors requires an integrative approach that is best accomplished by a team of health care professionals. It creates a significant challenge but one that must be met if allograft survival is to improve.

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St John's Wort Supplements Endanger the Success of Organ Transplantation

Cited by 106 publications

References 26 publications

Induction of Cytochrome P450 3A4 and P-Glycoprotein by the Isoxazolyl- Penicillin Antibiotic Flucloxacillin

Induction of Cytochrome P450 3A4 and P-Glycoprotein by the Isoxazolyl- Penicillin Antibiotic Flucloxacillin

Use of Herbal Products and Potential Interactions in Patients With Cardiovascular Diseases

Management of Cardiovascular Disease in Renal Transplant Recipients

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