Drug-Herb Interaction: Effect of St John’s Wort on Bioavailability and Metabolism of Procainamide in Mice (Report)

Drug-Herb Interaction: Effect of St John's Wort on Bioavailability and Metabolism of Procainamide in Mice (Report)

St John’s wort is a popular antidepressant available without a prescription from health food stores throughout the United States. According to a study on the use of herbal remedies in the United States, the most commonly used was ginseng followed by Echinacea, Ginkgo biloba, and St John’s wort. (1) Most commercially sold St John’s wort preparations in the United States are alcoholic or dried extract of hypericum, a perennial aromatic shrub. The main mechanisms of drug-herb interaction involve induction or inhibition of hepatic or intestinal metabolism of drugs by cytochrome P450 (CYP). CYP3A4 is the most abundant isoenzyme of CYP and is responsible for metabolism of more than 73 medications and numerous endogenous compounds. (2) The active components of St John’s wort induce CYP3A4 and other isoenzymes. (3-5) In particular, hyperforin is thought to be responsible for isoenzyme induction through activation of a nuclear steroid/pregnane and xenobiotic receptor. (6) Another mechanism of drug-herb interaction involves induction or inhibition of intestinal drug efflux pumps including P-glycoprotein and multiple resistance proteins. (7) St John’s wort also modulates P-glycoprotein drug transporter, and hypericin may be the active ingredient that is responsible for this effect. (8,9) Therefore, it is likely that St John’s wort will interact with drugs that are metabolized via CYP3A4 or where P-glycoprotein pumps play a role in disposition of the drug. (10) Self-medication with St John’s wort may cause treatment failures because of increase in clearance of many prescribed drugs. These include immunosuppressants (cyclosporine and tacrolimus), human immunodeficiency virus protease inhibitors, human immunodeficiency virus non-nucleoside reverse transcriptase inhibitors metabolized via CYP3A4, antineoplastic drugs such as irinotecan and imatinib mesylate, amitriptyline, digoxin, fexofenadine, benzodiazepines, theophylline, oral contraceptives, and warfarin. (11-14) Unrecognized use of St John’s wort is frequent and may have an important influence on the effectiveness and safety of drug therapy during hospital stays. (15)

Drug-Herb Interaction: Effect of St John's Wort on Bioavailability and Metabolism of Procainamide in Mice (Report)



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