No clinically relevant CYP3A induction after St. John's wort with low hyperforin content in healthy volunteers.
OBJECTIVE
Induction of CYP3A by St. John's wort (SJW) products with high hyperforin content is well described. Since CYP3A induction is mediated by hyperforin in a concentration-dependent manner, and SJW preparations differ significantly in hyperforin content, the aim of the study was to evaluate the effect of an SJW powder with low hyperforin content on CYP3A function.


METHODS
Twenty healthy male volunteers received an SJW powder with low hyperforin content for 2 weeks. Midazolam plasma concentration time profiles were characterized after a single oral dose of 7.5 mg midazolam on the day before and on the 14th day of SJW medication.


RESULTS
Midazolam AUC(0-infinity) slightly decreased from 124.0 +/- 62.5 ng/ml.h at baseline to 105.6 +/- 53.2 ng/ml.h after SJW (P < 0.05), representing a mean 11.3% decrease (95% CI: -22.8 to 0.21). No significant change in midazolam C(max), t(1/2) and t(max) was observed. For all pharmacokinetic parameters, the 90% CI for the geometric mean ratio of treatment over baseline were within the no-effect boundaries of 0.70-1.43.


CONCLUSIONS
Administration of an SJW product with low hyperforin content resulted in a mild induction of CYP3A not considered clinically relevant.
Mueller
Silke C
SC
Center of Pharmacology and Toxicology, Institute of Clinical Pharmacology, University of Rostock, Schillingallee 70, 18057 Rostock, Germany. silke.mueller@med.uni-rostock.de
Majcher-Peszynska
Jolanta
J
Mundkowski
Ralf G
RG
Uehleke
Bernhard
B
Klammt
Sebastian
S
Sievers
Hartwig
H
Lehnfeld
Romanus
R
Frank
Bruno
B
Thurow
Kerstin
K
Kundt
Guenther
G
Drewelow
Bernd
B