Studies On Pharmacokinetics Of Daidzein And Its Prodrugs

Daidzein (4',7-dihydroxylisoflavone) is one of the naturally occurring isoflavones mainly present in leguminous plants, especially in soybeans, soy foods and Pueraria lobata Ohwi (Leguminosae). There is a growing scientific interest in daidzein due to its potential beneficial effects for human health. Daidzein is used as a cardio- and cerebro-vascular drug for the therapy of hypertension, coronary heart disease and cerebro-thrombus diseases in China. Several epidemiological studies in humans have suggested that daidzein intake is inversely associated with the incidence of hormone-dependent diseases, especially breast and prostate cancer. In addition to its putative anticarcinogenic effects, daidzein has also been investigated as an antihyperlipidemic agent and a therapeutic substance to combat osteoporosis.In present paper, the pharmacokinetics and metabolism of daizein in rats were systematically investigated, and its prodrugs were synthesized in order to improve its oral bioavailability. The absorption mechanism of daidzein and its prodrugs were studied using n-octanol/buffer system, liposome/buffer system, immobilized artificial membrane chromatography and Caco-2 cell model. Studies on the pharmacokinetics of daidzein prodrugs were performed to screen out new drug candidates with better affinity to biological membrane and higher oral bioavailability.1. Studies on pharmacokinetics and metabolism of daidzein in ratsAn LC/MS/MS method was developed and validated for the determination of free daidzein in biological samples with genistein as the internal standard. The concentration of daidzein-7-O-glucuronide was calculated by the total concentration of daidzein after enzymatic hydrolysis by p-glucuronidase minus the concentration of free daidzein. The analytical method was optimized by the investigations on chromatographic conditions, mass spectrometric conditions, extraction methods, hydrolysis conditions, and selection of internal standard. The analyte and internal standard (genistein) were extracted from plasma samples by n-hexane-diethyl ether...