title: Different effects of St John's wort on the pharmacokinetics of simvastatin and pravastatin.
abstract: 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.
authors.affiliation: Department of Clinical Pharmacology, Jichi Medical School, Tochigi, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Sugimoto
authors.forename: M
authors.initials: M
authors.lastname: Ohmori
authors.forename: S
authors.initials: S
authors.lastname: Tsuruoka
authors.forename: K
authors.initials: K
authors.lastname: Nishiki
authors.forename: A
authors.initials: A
authors.lastname: Kawaguchi
authors.forename: K
authors.initials: K
authors.lastname: Harada
authors.forename: M
authors.initials: M
authors.lastname: Arakawa
authors.forename: K
authors.initials: K
authors.lastname: Sakamoto
authors.forename: M
authors.initials: M
authors.lastname: Masada
authors.forename: I
authors.initials: I
authors.lastname: Miyamori
authors.forename: A
authors.initials: A
authors.lastname: Fujimura
mesh_terms: D000328:Adult; D000924:Anticholesteremic Agents / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001711:Biotransformation; D002853:Chromatography, Liquid; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004347:Drug Interactions; D005260:Female; D006801:Humans; D020902:Hypericum / Q000009:adverse effects*; D008297:Male; D013058:Mass Spectrometry; D008517:Phytotherapy / Q000009:adverse effects*; D017035:Pravastatin / Q000493:pharmacokinetics*; D019821:Simvastatin / Q000493:pharmacokinetics*
chemical_list: D000924:Anticholesteremic Agents; D019821:Simvastatin; D017035:Pravastatin