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Effect of St John's wort dose and preparations on the pharmacokinetics of digoxin.
Clin Pharmacol Ther 2004; 75(6):546-57CP

Abstract

BACKGROUND AND 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+Show Affiliations

Center of Pharmacology and Toxicology, Institute of Clinical Pharmacology, University of Rostock, Rostock, Germany. silke.mueller@med.uni-rostock.deNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial
Comparative Study
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15179409

Citation

Mueller, Silke C., et al. "Effect of St John's Wort Dose and Preparations On the Pharmacokinetics of Digoxin." Clinical Pharmacology and Therapeutics, vol. 75, no. 6, 2004, pp. 546-57.
Mueller SC, Uehleke B, Woehling H, et al. Effect of St John's wort dose and preparations on the pharmacokinetics of digoxin. Clin Pharmacol Ther. 2004;75(6):546-57.
Mueller, S. C., Uehleke, B., Woehling, H., Petzsch, M., Majcher-Peszynska, J., Hehl, E. M., ... Drewelow, B. (2004). Effect of St John's wort dose and preparations on the pharmacokinetics of digoxin. Clinical Pharmacology and Therapeutics, 75(6), pp. 546-57.
Mueller SC, et al. Effect of St John's Wort Dose and Preparations On the Pharmacokinetics of Digoxin. Clin Pharmacol Ther. 2004;75(6):546-57. PubMed PMID: 15179409.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effect of St John's wort dose and preparations on the pharmacokinetics of digoxin. AU - Mueller,Silke C, AU - Uehleke,Bernhard, AU - Woehling,Heike, AU - Petzsch,Michael, AU - Majcher-Peszynska,Jolanta, AU - Hehl,Eva-Maria, AU - Sievers,Hartwig, AU - Frank,Bruno, AU - Riethling,Anne-Kathrin, AU - Drewelow,Bernd, PY - 2004/6/5/pubmed PY - 2004/7/9/medline PY - 2004/6/5/entrez SP - 546 EP - 57 JF - Clinical pharmacology and therapeutics JO - Clin. Pharmacol. Ther. VL - 75 IS - 6 N2 - BACKGROUND AND 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. SN - 0009-9236 UR - https://www.unboundmedicine.com/medline/citation/15179409/Effect_of_St_John's_wort_dose_and_preparations_on_the_pharmacokinetics_of_digoxin_ L2 - https://doi.org/10.1016/j.clpt.2004.01.014 DB - PRIME DP - Unbound Medicine ER -