Oral bioavailability of hyperforin from Hypericum extracts in rats and human volunteers

被引:168
作者
Biber, A
Fischer, H
Romer, A
Chatterjee, SS
机构
[1] Dr Willmar Schwabe Gmbh & Co, Dept Pharmacol, D-76209 Karlsruhe, Germany
[2] A&M Lab Analyt & Met Forsch Gmbh, Bergheim, Germany
关键词
D O I
10.1055/s-2007-979344
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Validated analytical methods suitable for determining hyperforin in plasma after administration of alcoholic Hypericum perforatum extracts containing hyperforin are described. After oral administration of 300 mg/kg Hypericum extract (WS 5572, containing 5% hyperforin) to rats maximum plasma levels of approximately 370 ng/ml (approx. 690 nM) were reached after 3 h, as quantified by a HPLC and UV detection method. Estimated half-life and clearance values were 6 h and 70 ml/min/kg respectively. Since therapeutic doses of Hypericum extracts are much lower than that used in rats, a more sensitive LC/MS/MS method was developed. The lower limit of quantification of this method was 1 ng/ml. Using this method, plasma levels of hyperforin could be followed for up to 24 h in healthy volunteers after administration of film coated tablets containing 300 mg hypericum extracts representing 14.8 mg hyperforin. The maximum plasma levels of approximately 150 ng/ml (approx. 280 nM) were reached 3.5 h after administration. Half-life and mean residence time were 9 and 12 h respectively. Hyperforin pharmacokinetics were linear up to 600 mg of the extract. Increasing the doses to 900 or 1200 mg of extract resulted in lower C-max and AUC values than those expected from linear extrapolation of data from lower doses. Plasma concentration curves in volunteers fitted well in an open two-compartment model. In a repeated dose study, no accumulation of hyperforin in plasma was observed. Using the observed AUC values from the repeated dose study, the estimated steady state plasma concentrations of hyperforin after 3 x 300 mg/day of the extract, i.e., after normal therapeutic dose regimen, was approximately 100 ng/ml (approx. 180 nM).
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页码:36 / 43
页数:8
相关论文
共 18 条
[1]   Hypericin and pseudohypericin: Pharmacokinetics and effects on photosensitivity in humans [J].
Brockmoller, J ;
Reum, T ;
Bauer, S ;
Kerb, R ;
Hubner, WD ;
Roots, I .
PHARMACOPSYCHIATRY, 1997, 30 :94-101
[2]   Effects of the total extract and fractions of hypericum perforatum in animal assays for antidepressant activity [J].
Butterweck, V ;
Wall, A ;
LieflanderWulf, U ;
Winterhoff, H ;
Nahrstedt, A .
PHARMACOPSYCHIATRY, 1997, 30 :117-124
[3]  
CHATTERJEE SS, 1998, IN PRESS LIFE SCI
[4]  
CHATTERJEE SS, 1996, PHYTOMEDICINE S1, V3, P106
[5]  
HANSEL R, 1993, HAGERS HDB PHARM PRA, V5, P474
[6]  
HOLZL J, 1994, PHARM ZTG, V139, P3959
[7]   ADVERSE DRUG-REACTIONS - CRITICAL REVIEW [J].
KARCH, FE ;
LASAGNA, L .
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 1975, 234 (12) :1236-1241
[8]   Single-dose and steady-state pharmacokinetics of hypericin and pseudohypericin [J].
Kerb, R ;
Brockmoller, J ;
Staffeldt, B ;
Ploch, M ;
Roots, I .
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 1996, 40 (09) :2087-2093
[9]   St. John's Wort in mild to moderate depression: The relevance of hyperforin for the clinical efficacy [J].
Laakmann, G ;
Schule, C ;
Baghai, T ;
Kieser, M .
PHARMACOPSYCHIATRY, 1998, 31 :54-59
[10]   ANALYSIS AND STABILITY OF HYPERICI OLEUM [J].
MAISENBACHER, P ;
KOVAR, KA .
PLANTA MEDICA, 1992, 58 (04) :351-354