CYP3A and P‐Glycoprotein Activity Induction With St. John's Wort in Healthy Volunteers From 6 Ethnic Populations

Xie, Ruiqin; Tan, Leonard; Polasek, Emery C.; Hong, Cassandra; Teillol-Foo, M.; Gordi, Toufigh; Sharma, Amarnath; Nickens, Dana; Arakawa, Tomoko; Knuth, Dean W.; Antal, Edward J.

doi:10.1177/0091270004273320

Cited by 52 publications

(37 citation statements)

References 18 publications

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“…Effects on CYP or P-glycoprotein after SJW treatment in the 4-9-day range are not available. In addition, the extent of CYP3A4 and P-glycoprotein induction was found to be comparable among a number of ethnic groups, namely Caucasians, Africans, Americans, Hispanics, Chinese, Indians, and Malays (27).…”

Section: Influence Of St John's Wort On Cytochrome P450 Enzymes and Pmentioning

confidence: 89%

“…Strong evidence from animal studies as well as preclinical and clinical studies suggests that SJW may modulate CYP activity. Using well-established probe drugs (e.g., alprazolam and midazolam for CYP3A4, caffeine for CYP1A2, chlorzoxazone for CYP2E1, dextromethorphan and debrisoquine for CYP2D6, tolbutamide for CYP2C9, and omeprazole for CYP2C19), a number of clinical trials have consistently shown that SJW induces CYP3A4, CYP2E1, and CYP2C19, with no effect on CYP1A2, CYP2D6, or CYP2C9 (16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30). Some authors have also suggested that SJW may induce CYP1A2 only in females (24).…”

Section: Influence Of St John's Wort On Cytochrome P450 Enzymes and Pmentioning

confidence: 99%

“…SJW has been shown to induce P-glycoprotein expression in intestinal isolated cells (33) as well as in the human intestine in healthy volunteers (34). Accordingly, SJW has been shown to lower plasma concentration of well-known P-glycoprotein substrates, including digoxin (35)(36)(37), fexofenadine (25,27), and talinolol (38). The effect on probe substrates was associated to increased MDR1 mRNA as well as P-glycoprotein levels in the human intestinal mucosa (38).…”

Section: Influence Of St John's Wort On Cytochrome P450 Enzymes and Pmentioning

confidence: 99%

“…The effect of SJW on P-glycoprotein or CYP enzymes is generally observed after long treatment [ten or more days (25,27,35,39); data with treatment for lesser numbers of days (i.e., 4-9 days) are not available] with studies reporting no effect (or even nonclinically relevant stimulating effects) following acute (1-3 days) SJW administration (19,40). Effects on CYP or P-glycoprotein after SJW treatment in the 4-9-day range are not available.…”

Section: Influence Of St John's Wort On Cytochrome P450 Enzymes and Pmentioning

confidence: 99%

“…Experimentally, fexofenadine is used as probe substrate for P-glycoprotein. Two clinical trials showed that SJW affected the pharmacokinetics of fexofenadine (25,27). Dresser and colleagues found that 12 days' treatment with SJW increased the oral clearance of fexofenadine in 21 young healthy subjects (25).…”

Section: Drugs Acting On the Respiratory Systemmentioning

confidence: 99%

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Herb–Drug Interactions with St John’s Wort (Hypericum perforatum): an Update on Clinical Observations

Borrelli

Izzo

2009

AAPS J

238

190

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Abstract. St John's wort (SJW) extracts, prepared from the aerial parts of Hypericum perforatum, contain numerous pharmacologically active ingredients, including naphthodianthrones (e.g., hypericin and its derivatives), phloroglucinols derivatives (e.g., hyperforin, which inhibits the reuptake of a number of neurotransmitters, including serotonin), and flavonoids. Such extracts are widely used for the treatment of mild-to-moderate depression. As a monotherapy, SJW has an encouraging safety profile. However, relevant and, in some case, life-threatening interactions have been reported, particularly with drugs which are substrate of cytochrome P450 and/or P-glycoprotein. Well-documented SJW interactions include (1) reduced blood cyclosporin concentration, as suggested by multiple case reports as well as by clinical trials, (2) serotonin syndrome or lethargy when SJW was given with serotonin reuptake inhibitors, (3) unwanted pregnancies in women while using oral contraceptives and SJW, and (4) reduced plasma drug concentration of antiretroviral (e.g., indinavir, nevirapine) and anticancer (i.e., irinotecan, imatinib) drugs. Hyperforin, which is believed to contribute to the antidepressant action of St John's wort, is also strongly suspected to be responsible of most of the described interactions.

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Section: Influence Of St John's Wort On Cytochrome P450 Enzymes and Pmentioning

confidence: 89%

Section: Influence Of St John's Wort On Cytochrome P450 Enzymes and Pmentioning

confidence: 99%

Section: Influence Of St John's Wort On Cytochrome P450 Enzymes and Pmentioning

confidence: 99%

Section: Influence Of St John's Wort On Cytochrome P450 Enzymes and Pmentioning

confidence: 99%

Section: Drugs Acting On the Respiratory Systemmentioning

confidence: 99%

See 3 more Smart Citations

Herb–Drug Interactions with St John’s Wort (Hypericum perforatum): an Update on Clinical Observations

Borrelli

Izzo

2009

AAPS J

238

190

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Introduction to Drug Transporters

Leung¹,

Oganesian²

2008

Drug Metabolism Handbook

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Introduction to Drug Transporters

Leung¹,

Oganesian²

2010

Pharmaceutical Sciences Encyclopedia

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The role of transporter proteins in drug and endogenous substance disposition has increasingly gained recognition over the last decade. Inhibition or induction of different drug transporters in different tissues can lead to clinical drug‐drug interactions that may result in adverse effects or lack of efficacy. The article offers insights into the role of drug transporters in drug development, drug absorption, metabolism, and toxicity.

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CYP3A and P‐Glycoprotein Activity Induction With St. John's Wort in Healthy Volunteers From 6 Ethnic Populations

Cited by 52 publications

References 18 publications

Herb–Drug Interactions with St John’s Wort (Hypericum perforatum): an Update on Clinical Observations

Herb–Drug Interactions with St John’s Wort (Hypericum perforatum): an Update on Clinical Observations

Introduction to Drug Transporters

Introduction to Drug Transporters

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