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Different effects of St John's Wort on the pharmacokinetics of simvastatin
and pravastatin
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(Clin Pharmacol Ther 2001;70:518-24.)
Objective: St John's Wort, a widely used herbal product, is an inducer of
CYP3A4 and it decreases blood concentrations of CYP3A4 substrates. The
effects of St John's Wort on the pharmacokinetics of
3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors simvastatin (an
inactive lactone pro-drug) and pravastatin were determined in this study.
Methods: Sixteen healthy male subjects (n = 8 in group 1 and n = 8 in group
2) took a St John's Wort caplet (300 mg) or matching placebo three times a
day for 14 days in a double-blind, crossover study. On day 14, a single oral
dose of 10 mg simvastatin and 20 mg pravastatin was given to subjects in
group 1 and group 2, respectively. Blood samples were obtained during a
24-hour period after the administration of each drug.
Results: Repeated St John's Wort treatment tended to lower plasma simvastatin
concentration and significantly (P < .05) lowered concentrations of
simvastatin hydroxy acid, its active metabolite. The peak concentration in
plasma (ratio, 0.72 of placebo) of simvastatin hydroxy acid tended to be
decreased and its area under the plasma concentration-time curve between time
zero and 24 hours after administration (ratio, 0.48 of placebo) was
significantly decreased (P < .05) by St John's Wort. On the other hand, St
John's Wort did not influence plasma pravastatin concentration. No
significant differences were observed in the elimination half-life of
simvastatin or pravastatin between the placebo and St John's Wort trials.
Conclusions: This study showed that St John's Wort decreases plasma
concentrations of simvastatin but not of pravastatin. Because simvastatin is
extensively metabolized by CYP3A4 in the intestinal wall and liver, which are
induced by St John's Wort, it is likely that this interaction is partly
caused by the enhancement of the CYP3A4-mediated first-pass metabolism of
simvastatin in the small intestine and liver.
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