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Comparing the pharmacokinetics of daidzein and genistein with the use of ¹³C-labeled tracers in premenopausal women^1,2,3

¹ From Clinical Mass Spectrometry, Children’s Hospital Medical Center, Cincinnati (KDRS, LZ-N, NMB, BEW, and WTB); the School of Biomedical and Life Sciences, University of Surrey, Guildford, United Kingdom (MSF, TA, and AC); the College of Pharmacy, University of Cincinnati College of Medicine (PD); and the University of St Andrews, School of Chemistry, St Andrews, Fife, United Kingdom (MFO and NPB).

Background: Despite significant interest in the risks and benefits of phytoestrogens to human health, few data exist on their pharmacokinetics in humans.

Objective: We investigated the pharmacokinetics of the ¹³C isotopic forms of daidzein and genistein in healthy humans, specifically addressing intraindividual variability, effect of increasing intake, and influence of prolonged exposure to a soy food diet.

Design: Premenopausal women (n = 16) were administered 0.4 mg [¹³C]daidzein or [¹³C]genistein/kg body wt orally on 3 occasions, including once after eating soy foods for 7 d. On a further occasion the dose was doubled. Plasma and urinary [¹³C]isoflavone concentrations were measured by mass spectrometry.

Results: Serum concentrations of [¹³C]genistein and [¹³C]daidzein peaked after 5.5 and 7.4 h, respectively. The systemic bioavailability and maximum serum concentration of [¹³C]genistein were significantly greater than those of [¹³C]daidzein. The bioavailability of both isoflavones did not increase linearly when the dietary intake was doubled. The mean volume of distribution normalized to bioavailability (V_d/F), clearance rate, and half-life of [¹³C]daidzein were 336.25 L, 30.09 L/h, and 7.75 h, respectively; the corresponding values for [¹³C]genistein were 258.76 L, 21.85 L/h, and 7.77 h. The average recovery of [¹³C]daidzein and [¹³C]genistein in urine was 30.1% and 9.0% of the dose ingested, respectively.

Conclusions: The serum pharmacokinetics of [¹³C]daidzein and [¹³C]genistein were reproducible among healthy women, and genistein was more bioavailable than was daidzein. Pharmacokinetics were unaffected by chronic exposure to soy foods. Urinary isoflavone concentrations correlated poorly with maximal serum concentrations, indicating the limitations of urine measurements as a predictor of systemic bioavailability. The bioavailability of both isoflavones was nonlinear at higher intakes, suggesting that uptake is rate-limiting and saturable.

Key Words: Isoflavones • pharmacokinetics • stable isotopes • bioavailability • absorption • metabolism • women • phytoestrogens • daidzein • genistein • soy foods

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