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Investigation of the Bioavailability of Hypericin, Pseudohypericin, Hyperforin and the Flavonoids Quercetin and Isorhamnetin Following Single and Multiple Oral Dosing of a Hypericum Extract Containing Tablet

2011; Thieme Medical Publishers (Germany); Volume: 55; Issue: 01 Linguagem: Inglês

10.1055/s-0031-1296820

1616-7066

Hans‐Ulrich Schulz, Michael Schürer, Dagmar Bässler, D Weiser,

Natural Compound Pharmacology Studies

The objective of these two open phase I clinical trials was the investigation of the bioavailability of five constituents from a hypericum extract containing tablet, which are discussed as the components contributing to the antidepressant action. Each trial included 18 healthy male volunteers who received the test preparation, containing 612 mg dry extract of St John's wort (STW-3, Laif® 600), either as a single oral dose or as a multiple once daily dose over a period of 14 days. Concentration/time curves were determined for hypericin, pseudohypericin, hyperforin, the flavonoid aglycone quercetin, and its methylated form isorhamnetin for 48 h after single dosing and for 24 h on day 14 at the end of 2 weeks of continuous daily dosing. After single dose intake, the key pharmacokinetic parameters were determined as follows: hypericin: area under the curve (AUC( 0–" )) = 75.96 h · ng/ml, maximum plasma concentration (C max ) = 3.14 ng/ml, time to reach C max (t max ) = 8.1 h, and elimination half-life (t1/2) = 23.76 h; pseudohypericin: AUC( 0∞ ) = 93.03 h · ng/ml, C max = 8.50 ng/ml, t max = 3.0 h, t1/2 = 25.39 h; hyperforin: AUC( 0–∞ ) = 1009.0 h · ng/ml, C max = 83.5 ng/ml, t max = 4.4 h, t 1/2 = 19.64 h. Quercetin and isorhamnetin showed two peaks of maximum plasma concentration separated by about 4 h. Quercetin: AUC( 0→ ) = 318,7 h · ng/ml, C max (1) =ng/ml, t max (1) = 1.17 h, C max (2) =ng/ml, t max (2) = 5.47 h, t 1/2 = 4.16 h; isorhamnetin: AUC (0–>) = 98.0 h · ng/ml, C max (1) = 7.6 ng/ml, t max (1) = .53 h, C max (2) = 9.0 ng/ml, t max (2) = 6.42 h, t 1/2 = 4.45 h. Under steady state conditions reached during multiple dose administration similar results were obtained. Further pharmacokinetic characteristics calculated from the obtained data were the mean residence time (MRT), the lag-time, the peak-trough fluctuation (PTF), the lowest observed plasma concentration (C min ), and the average plasma concentration (C av ). The data obtained for hypericin, pseudohypericin and hyperforin generally corresponded well with values previously published, with some deviations observed for the extent of absorption of hypericin and the time course of absorption and elimination of hyperforin. The kinetic characteristics of the hypericum flavonoids are reported here for the first time. The trial preparation was well tolerated.