Urinary pharmacokinetics of the glucuronide and sulfate conjugates of genistein and daidzein

Consumption of soybean-rich diets is thought to provide significant health benefits such as prevention of cancer, primarily because of the high conten ts of factors such as the isoflavones genistein and daidzein. Isoflavones c irculate and are excreted into the urine mainly as glucuronide and sulfate conjugates. This study was conducted to determine the urinary pharmacokinet ics of sulfate and glucuronide conjugates of genistein and daidzein. Twelve volunteers consumed a soy beverage providing 1 and 0.6 mg/kg body weight o f genistein and daidzein equivalents, respectively. Urine was collected at various times during the 48 h after soy consumption and was digested with e ither glucuronidase or sulfatase, and the liberated aglycones were extracte d and analyzed by liquid chromatopraphy-mass spectrometry. Urinary isoflavo ne sulfate levels were determined by two methods: (a) assessment of aglycon e after sulfatase hydrolysis (measured); or (b) calculated by subtracting t he aglycone + glucuronide levels from the total urinary isoflavone levels. The apparent terminal half-life for daidzein sulfate (3.9 +/- 0.5 h) that w as determined from sulfatase-treated urine was 32% shorter (P less than or equal to 0.02) than that of the calculated daidzein sulfate (5.7 +/- 0.08 h ). A similar trend was obtained for genistein sulfate (4.5 +/- 0.7 versus 6 .8 +/- 0.1 h). The apparent terminal half-lives for genistein and daidzein glucuronides were 6.0 +/- 0.4 and 3.8 +/- 0.4 h, respectively. These data s uggest that the measured urinary isoflavone sulfate values provide a better understanding of the pharmacokinetics than the calculated values. Addition al studies are needed to determine whether the apparent terminal half-lives can be attributed to elimination or absorption processes.