Single-dose and steady-state pharmacokinetics of hypericin and pseudohypericin

Abstract

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.

Johanniskraut (Hypericum perforatum L.) Eine Pflanze mit Relevanz für die Dermatologie

“…Die Substanzen werden rasch resorbiert (maximale Plasmaspiegel nach 2-6 h) und in einer nicht linearen Kinetik eliminiert. Die Halbwertszeiten betragen ungefähr 15 (Hyperforin) bis 30 (Hypericine) Stunden [4,9,25,53,57].…”

“…Im Gegensatz zur fehlenden Photosensibilisierung bei Einnahme von Johanniskrautextrakt kam es in einer Studie, bei der HIV-infizierte Patienten mit reinem Hypericin oral oder intravenös behandelt wurden, bei fast allen Patienten zu schweren phototoxischen Symptomen [19].Verschiedene pharmakokinetische Untersuchungen lassen darauf schließen,dass der phototoxische Schwellenwert von Hypericin durch orale Einnahme antidepressiver Johanniskrautextrakte bei weitem nicht erreicht wird [9,25,47,53].In diesen Studien lagen die maximalen Serumspiegel für Hypericin zwischen 12 und 61 ng/ml (Tabelle 2).…”

[Methyl-D3]2hypericin as internal standard for quantification in human plasma

“…pills or drops). Thus, the expected hypericin concentrations in blood are in the range of 1 to 10 ng mL -1 [21,22,23]. In the case of a higher dosage, higher levels of hypericin in blood are likely [24].…”

St. John's wort (Hypericum perforatum): a review of the current pharmacological, toxicological, and clinical literature

“…Pharmacokinetic studies in humans have revealed that clinically relevant dosages of total hypericin (approximately 1 mg/day) reach a maximal plasma concentration in the nanomolar to micromolar range after 4-6 h, and achieve a steady-state after about 4 days (Brockmöller et al 1997;Kerb et al 1996;Staffeldt et al 1994;Upton et al 1997). The absorptive lag-time is roughly twice as long for hypericin (approximately 2 h) versus pseudohypericin (approximately 1 h), and elimination of both compounds is reported to be slow; approximately 25 and 40 h, respectively (Staffeldt et al 1994).…”