Single-dose and steady-state pharmacokinetics of hypericin and pseudohypericin.
Single-dose and steady-state pharmacokinetics of antivirally acting hypericin (H) and pseudohypericin (PH) were studied in 13 healthy volunteers by administration of St. John's Wort extract LI 160, a plantal antidepressant. Oral administration of 250, 750, and 1,500 micrograms of H and 526, 1,578, and 3,156 micrograms of PH resulted in median peak levels in plasma (Cmax) of 1.3, 7.2, and 16.6 micrograms/liter for H and 3.4, 12.1, and 29.7 micrograms/liter for PH, respectively. The Cmax and the area under the curve values for the lowest dose were disproportionally lower than those for the higher doses. A lag time of 1.9 h for H was remarkably longer than the 0.4-h lag time for PH. Median half-lives for absorption, distribution, and elimination were 0.6, 6.0, and 43.1 h after 750 micrograms of H and 1.3, 1.4, and 24.8 h after 1,578 micrograms of PH, respectively. Fourteen-day treatment with 250 micrograms of H and 526 micrograms of PH three times a day resulted in median steady-state trough levels of 7.9 micrograms/liter for H and 4.8 micrograms/liter for PH after 7 and 4 days, respectively; the corresponding Cssmax levels were 8.8 and 8.5 micrograms/liter, respectively. Kinetic parameters after intravenous administration of Hypericum extract (115 and 38 micrograms for H and PH, respectively) in two subjects corresponded to those estimated after an oral dosage. Both H and PH were initially distributed into a central volume of 4.2 and 5.0 liter, respectively. The mean distribution volumes at steady state were 19.7 liters for H and 39.3 liters for PH, and the mean total clearance rates were 9.2 ml/min for H and 43.3 ml/min for PH. The systemic availability of H and PH from LI 160 was roughly estimated to be 14 and 21%, respectively. Treatment with Hypericum extract, even in high doses, was well tolerated.
Kerb
R
R
Institute of Clinical Pharmacology, University Clinic Charité, Humboldt University of Berlin, Germany.
Brockmöller
J
J
Staffeldt
B
B
Ploch
M
M
Roots
I
I
D000284:Administration, Oral; D000328:Adult; D000873:Anthracenes; D000998:Antiviral Agents / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D019540:Area Under Curve; D001835:Body Weight; D002851:Chromatography, High Pressure Liquid; D004311:Double-Blind Method; D006207:Half-Life; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D010569:Perylene / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics / Q000652:urine
D000873:Anthracenes; D000998:Antiviral Agents; D010569:Perylene; C004965:hypericin; C056602:pseudohypericin