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St John's Wort May Reduce Bioavailability of Conventional Medications

Conventional drugs may show reduced systemic bioavailability when taken concomitantly with Hypericum perforatum, the herbal supplement commonly known as St John's wort.

Edward Mills, graduate fellow, Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada, and colleagues systematically reviewed prospective clinical trials that assessed pharmacokinetic effect of St John's wort on the metabolism of a conventional drug.

The conventional drugs in the 22 pharmacokinetic trials analysed included irinotecan, dextromethorphan and alprazolam, carbamazepine, digoxin, indinavir, tacrolimus and mycophenic acid or tacrolimus alone, cyclosporin A, oral contraceptives, midazolam, warfarin, amitriptyline, fexofenadine, simvastatin or pravastatin, omeprazole, and theophylline.

"The methodological quality of the included studies was limited," the authors note.

Overall, 18 of the studies did not have a control group. Of the 4 with control groups, 3 were randomised but did not describe the randomisation procedure, while 3 control groups received placebo but the placebo was not described. The studies were generally small with an average of 12 participants per study. Independent assays to determine the dosage of the St John's wort preparation occurred in 15 of the studies.

The investigators assessed the magnitude of the interaction between St John's wort and the conventional drug by differences in the area under the curve (AUC) of the drug before and after challenge with St. John's wort. In the 19 trials with data on the systemic bioavailability of the conventional drugs in plasma, data from 15 reveals a decrease of greater than 20%.

"Our review shows that St John's wort has the potential to reduce systemic bioavailability of many conventional drugs," the authors conclude, adding that clinicians and patients should be aware of this possibility. "Higher quality research is necessary to provide reliable information to guide clinical practice," they note.

BMJ 2004;329:27-30, doi:10.1136/bmj.329.7456.27

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