Effect of St John's wort dose and preparations on the pharmacokinetics of digoxin.
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.
Mueller
Silke C
SC
Center of Pharmacology and Toxicology, Institute of Clinical Pharmacology, University of Rostock, Rostock, Germany. silke.mueller@med.uni-rostock.de
Uehleke
Bernhard
B
Woehling
Heike
H
Petzsch
Michael
M
Majcher-Peszynska
Jolanta
J
Hehl
Eva-Maria
EM
Sievers
Hartwig
H
Frank
Bruno
B
Riethling
Anne-Kathrin
AK
Drewelow
Bernd
B
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
D010936:Plant Extracts; D011208:Powders; D013608:Tablets, Enteric-Coated; D013662:Tea; D004077:Digoxin