title: Effect of St John's wort dose and preparations on the pharmacokinetics of digoxin.
abstract: OBJECTIVE
  St John's wort preparations vary in composition, main constituents, formulation, and daily dose administered. The aim of the study was to evaluate the possible pharmacokinetic interaction of marketed St John's wort formulations and doses with digoxin.
  
  
  METHODS
  A randomized, placebo-controlled, parallel-group study was performed in 96 healthy volunteers in 3 study parts. A 7-day loading phase with digoxin was followed by 14 days of comedication with placebo or one of 10 St John's wort products varying in dose and formulation. The pharmacokinetics of digoxin was determined before comedication and on day 14 of comedication.
  
  
  RESULTS
  Comedication comprised traditionally used Hypericum products; 2 g powder without hyperforin, tea, juice, oil extract, and placebo had no significant interaction with digoxin nor did hyperforin-free extract (Ze 117) or low daily doses of hyperforin-containing Hypericum powder (1 g, 0.5 g). However, comedication with the high-dose hyperforin-rich extract LI 160 resulted in a reduction of digoxin area under the curve from time 0 to 24 hours (AUC(0-24)) of -24.8% (95% confidence interval [CI], -28.3 to -21.3), a reduction in digoxin maximal plasma concentration (C(max)) of -37% (95% CI, -42 to -32), and a reduction in digoxin plasma concentration at 24 hours after previous dosing (C(trough)) of -19% (95% CI, -27 to -11). Comedication with 4 g Hypericum powder with comparable hyperforin content resulted in a reduction in digoxin AUC(0-24) of -26.6% (95% CI, -37.3 to -15.9), a reduction in digoxin C(max) of -38% (95% CI, -48 to -18), and a reduction in digoxin C(trough) of -19% (95% CI, -27 to -10). Two grams of Hypericum powder with half the hyperforin content resulted in a less prominent reduction in AUC(0-24) of -17.7% (95% CI, -21.6 to -13.7), C(max) (-21%; 95% CI, -40 to -2), and C(trough) (-13%; 95% CI, -21 to -5).
  
  
  CONCLUSIONS
  The interaction of St John's wort and digoxin varies within St John's wort preparations and doses and seems to be correlated with the dose, particularly of hyperforin.
authors.affiliation: Center of Pharmacology and Toxicology, Institute of Clinical Pharmacology, University of Rostock, Rostock, Germany. silke.mueller@med.uni-rostock.de
authors.forename: Silke C
authors.initials: SC
authors.lastname: Mueller
authors.forename: Bernhard
authors.initials: B
authors.lastname: Uehleke
authors.forename: Heike
authors.initials: H
authors.lastname: Woehling
authors.forename: Michael
authors.initials: M
authors.lastname: Petzsch
authors.forename: Jolanta
authors.initials: J
authors.lastname: Majcher-Peszynska
authors.forename: Eva-Maria
authors.initials: EM
authors.lastname: Hehl
authors.forename: Hartwig
authors.initials: H
authors.lastname: Sievers
authors.forename: Bruno
authors.initials: B
authors.lastname: Frank
authors.forename: Anne-Kathrin
authors.initials: AK
authors.lastname: Riethling
authors.forename: Bernd
authors.initials: B
authors.lastname: Drewelow
mesh_terms: D000293:Adolescent; D000328:Adult; D019540:Area Under Curve; D002626:Chemistry, Pharmaceutical; D016001:Confidence Intervals; D004077:Digoxin / Q000493:pharmacokinetics*; D004311:Double-Blind Method; D004347:Drug Interactions; D005260:Female; D006801:Humans; D020902:Hypericum / Q000378:metabolism*; D008297:Male; D010936:Plant Extracts / Q000008:administration & dosage / Q000493:pharmacokinetics; D011208:Powders; D013608:Tablets, Enteric-Coated; D013662:Tea / Q000378:metabolism
chemical_list: D010936:Plant Extracts; D011208:Powders; D013608:Tablets, Enteric-Coated; D013662:Tea; D004077:Digoxin