Pharmacokinetics of 23-epi-26-deoxyactein in women after oral administration of a standardized extract of black cohosh.
Dietary supplements containing black cohosh are alternatives to conventional hormone replacement therapy in menopause. This study investigates the maximum tolerated dose of a 75% ethanol extract of black cohosh and determines the pharmacokinetics of one of its most abundant triterpene glycosides, 23-epi-26-deoxyactein. Single doses of black cohosh extract containing 1.4, 2.8, or 5.6 mg of 23-epi-26-deoxyactein were administered to 15 healthy, menopausal women. Serial blood samples and 24-h urine samples were obtained; blood chemistry, hormonal levels, and 23-epi-26-deoxyactein levels were determined. No acute toxicity or estrogenic hormone effects were observed. Pharmacokinetic analyses of 23-epi-26-deoxyactein in sera indicated that the maximum concentration and area under the curve increased proportionately with dosage, and that the half-life was ~2 h for all dosages. Less than 0.01% of the 23-epi-26-deoxyactein was recovered in urine 24 h after administration. No phase I or phase II metabolites were observed either in clinical specimens or in vitro.
van Breemen
R B
RB
UIC/NIH Center for Botanical Dietary Supplements Research, University of Illinois College of Pharmacy, Department of Medicinal Chemistry and Pharmacognosy, Chicago, Illinois, USA. breemen@uic.edu
Liang
W
W
Banuvar
S
S
Shulman
L P
LP
Pang
Y
Y
Tao
Y
Y
Nikolic
D
D
Krock
K M
KM
Fabricant
D S
DS
Chen
S-N
SN
Hedayat
S
S
Bolton
J L
JL
Pauli
G F
GF
Piersen
C E
CE
Krause
E C
EC
Geller
S E
SE
Farnsworth
N R
NR
D000284:Administration, Oral; D019540:Area Under Curve; D031885:Cimicifuga / Q000737:chemistry*; D019587:Dietary Supplements; D004305:Dose-Response Relationship, Drug; D005260:Female; D006207:Half-Life; D006801:Humans; D020714:Maximum Tolerated Dose; D008593:Menopause; D008875:Middle Aged; D010936:Plant Extracts / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D012503:Saponins / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D014315:Triterpenes / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*
D010936:Plant Extracts; D012503:Saponins; D014315:Triterpenes; C457248:23-epi-26-deoxyactein