Study 11

Pharmacokinetics of hypericin and pseudohypericin after oral intake of the Hypericum perforatum extract LI 160 in healthy volunteers

AU: Staffeldt-B; Kerb-R; Brockmoller-J; Ploch-M; Roots-I

AD: Institut fur Klinische Pharmakologie, Universitatsk-linikum Charite Berlin, Germany.

SO: J-Geriatr-Psychiatry-Neurol. 1994 Oct; 7 Suppl 1: S47-53

Setup

The single- and multiple-dose pharmacokinetics of hypericin and pseudohypericin were studied in 12 healthy malesubjects. After a single oral dose of 300, 900, or 1800 mg of dried hypericum extract (250, 750, or 1500 micrograms hypericin and 526, 1578, or 3156 micrograms pseudohypericin and 900, 2700, and 5400 microg. total hypericin), plasma levels were measured up to 3 days.

Some facts about the flower Hypericum perforatum and its content of hypericin

The hypericum extract was taken from the upper parts of Hypericum perforatum L just before or during the blossoming. It has been found that the concentrations of hypericin can vary with a factor of 10 between individual plants.

Table 8 gives a summary of the contents and concentration of important substances in a selection of the blooms of 50 hypericum plants.

Table 8

Constituent	Content in %
Hypericine	0.086
Pseudohypericin	0.23
Hyperforin	2.80
Biapigenin	0.26
Rutin	0.28
Hyperoside	0.66
Isoquercitrin	0.31
Quercitrin	0.34

Click Here for Index of Charts & Tables

Results

• The median maximal plasma levels were 1.5, 4.1, and 14.2 ng/ml for hypericin and 2.7, 11.7, and 30.6 ng/ml for pseudohypericin, respectively, for the three doses given above (interim evaluation of four volunteers).
• The median elimination half-life times of hypericin were 24.8 to 26.5 hours, and varied for pseudohypericin from 16.3 to 36.0 hours.
• Ranging between 2.0 to 2.6 hours, the median lag-time of absorption was remarkably prolonged for hypericin when compared to pseudohypericin (0.3 to 1.1 hours).
• The areas under the curves (AUC) showed a nonlinear increase with raising dose; this effect was statistically significant for hypericin.
• During long-term dosing (3 x 300 mg/day), a steady-state was reached after 4 days.
• Mean maximal plasma level during the steady-state treatment was 8.5 ng/ml for hypericin and 5.8 ng/ml for pseudohypericin, while mean trough levels were 5.3 ng/ml for hypericin and 3.7 ng/ml for pseudohypericin.
• In spite of their structural similarities, there are substantial pharmacokinetic differences between hypericin and pseudohypericin.