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 mu g of H and 526, 1,578, and 3,156 mu g of PH resulted in median peak levels in plasma (C-max) of 1.3, 7.2, and 16.6 mu g/liter for H and 3.4, 12.1, and 29.7 mu g/liter for PH, respectively, The C-max 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 mu g of H and 1.3, 1.4, and 24.8 h after 1,578 (mu g of PH, respectively, Fourteen-day treatment with 250 mu g of H and 526 mu g of PH three times a day resulted in median steady-state trough levels of 7.9 mu g/liter for H and 4.8 mu g/liter for PH after 7 and 4 days, respectively; the corresponding C-max(ss) levels were 8.8 and 8.5 mu g/liter, respectively, Kinetic parameters after intravenous administration of Hypericum extract (115 and 38 mu g 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.