Safety and pharmacokinetics of purified soy isoflavones: single-dose administration to postmenopausal women.
BACKGROUND
Soy isoflavones are being evaluated as chemopreventive agents for breast and other cancers.


OBJECTIVE
The objective was to perform safety and pharmacokinetic studies of purified unconjugated isoflavone preparations containing genistein, daidzein, and glycitein in postmenopausal women.


METHODS
Twenty-four healthy postmenopausal women ingested a single dose of 1 of 2 purified (from soybeans) isoflavone preparations that delivered a genistein dose of 2, 4, 8, or 16 mg/kg body wt. These doses were higher than those previously administered to human females. Toxicity studies were performed 24 h and 3, 6, 14, and 30 d after isoflavone administration. Kinetic studies were performed during the first 24 h.


RESULTS
We observed a 7% decrease in systolic and diastolic blood pressure and a 32% decrease in the neutrophil count 24 h after treatment with formulation A. Isolated episodes of nausea, pedal edema, and breast tenderness were judged to be possibly related to the study treatment. The terminal plasma half-lives for free genistein, daidzein, and glycitein averaged 3.8, 7.7, and 3.4 h, respectively. The terminal pseudo half-lives for total genistein and total daidzein in plasma averaged 10.1 and 10.8 h, respectively. The estimated bioavailabilities of both total genistein and total daidzein from each of the 2 formulations were not significantly different.


CONCLUSIONS
A single-dose administration of purified unconjugated isoflavones at amounts that exceed normal dietary intakes had minimal clinical toxicity in healthy postmenopausal women. The pharmacokinetic data suggest that chronic dosing at 12-24-h intervals would not lead to progressive accumulation of these isoflavones.
Bloedon
LeAnne T
LT
Department of Nutrition, School of Public Health, School of Medicine, University of North Carolina, Chapel Hill 27599-7400, USA.
Jeffcoat
A Robert
AR
Lopaczynski
Wlodek
W
Schell
Michael J
MJ
Black
Tracy M
TM
Dix
Kelly J
KJ
Thomas
Brian F
BF
Albright
Craig
C
Busby
Marjorie G
MG
Crowell
James A
JA
Zeisel
Steven H
SH
D000368:Aged; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D005260:Female; D019833:Genistein / Q000097:blood / Q000652:urine; D006207:Half-Life; D006801:Humans; D007529:Isoflavones / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology / Q000652:urine; D008875:Middle Aged; D017698:Postmenopause / Q000187:drug effects* / Q000378:metabolism*; D013025:Glycine max / Q000737:chemistry*
D004338:Drug Combinations; D007529:Isoflavones; C004742:daidzein; C086566:glycitein; D019833:Genistein