The extent of induction of CYP3A by St. John's wort varies among products and is linked to hyperforin dose.
OBJECTIVE
Induction of CYP3A by St. John's wort (SJW) extracts with high hyperforin (HYF) content is well described. Since SJW products vary in the amount of HYF and other main constituents, the aim of the study was to evaluate the effect on CYP3A function of SJW preparations with a range from very low to high HYF content.


METHODS
Forty-two male, healthy volunteers were randomized into six parallel SJW medication groups with varying composition especially with regard to HYF content. Midazolam plasma concentration 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
All SJW preparations tested resulted in a decrease in midazolam AUC, although the extent of the effect differed. The extract LI 160 (HYF 41 mg/day) decreased midazolam AUC0-12h by 79.4% (95% CI -88.6; -70.1), which was significantly greater than the effect by any other medication (p<0.05). SJW powder tablets 2.7 g/day (HYF 12 mg/day) resulted in a midazolam AUC0-12h decrease of 47.9% (95% CI -59.7;-36.2), while 2.7 g/day SJW powder tablets that were almost devoid of HYF (0.13 mg/day) reduced midazolam AUC0-12h by only 21.1% (95% CI -33.9; -8.3). Considering all six SJW medications tested, the extent of midazolam AUC decrease correlated significantly with increasing HYF dose (r=-0.765, p<0.001), but not with hypericin dose (r=-0.067; p=0.673).


CONCLUSIONS
The extent of induction of CYP3A varies among St. John's wort products and depends on hyperforin dose.
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
Uehleke
Bernhard
B
Klammt
Sebastian
S
Mundkowski
Ralf G
RG
Miekisch
Wolfram
W
Sievers
Hartwig
H
Bauer
Steffen
S
Frank
Bruno
B
Kundt
Guenther
G
Drewelow
Bernd
B
D000328:Adult; D019540:Area Under Curve; D001643:Bridged Bicyclo Compounds / Q000008:administration & dosage / Q000494:pharmacology; D051544:Cytochrome P-450 CYP3A / Q000096:biosynthesis*; D041743:Herb-Drug Interactions; D006801:Humans; D020902:Hypericum; D008297:Male; D008874:Midazolam / Q000493:pharmacokinetics*; D010696:Phloroglucinol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D010936:Plant Extracts / Q000494:pharmacology; D013607:Tablets; D013729:Terpenes / Q000008:administration & dosage / Q000494:pharmacology*
D001643:Bridged Bicyclo Compounds; D010936:Plant Extracts; D013607:Tablets; D013729:Terpenes; D010696:Phloroglucinol; D051544:Cytochrome P-450 CYP3A; D008874:Midazolam; C001654:hyperforin