Although isoflavones are capable of inducing genetic damage in vitro, a similar effect was not observed in subjects treated with a purified soy unconjugated isoflavone mixture.

A phase I clinical trial was conducted to determine the safety, pharmacokinetic parameters, and efficacy of orally administered isoflavones (genistein and daidzein, potential cancer chemotherapeutic agents) over a 3-mo period in men with prostate neoplasia. Twenty men, ages 40 and above, with stage B, C, or D adenocarcinoma of the prostate were treated with a multiple-dose regimen of a soy isoflavone formulation (delivering approximately 300 or 600 mg/day genistein and half this much daidzein) for 84 days. The delivered dose of isoflavones was more than 10-fold higher than that typically taken by prostate cancer patients. In men with prostate cancer, relatively minor side effects of chronic isoflavone treatment were observed including some estrogenic effects (breast changes, increased frequency of hot flashes). Serum dehydroepiandrosterone was decreased by 31.7% (P = 0.0004) at the end of treatment. Except for those subjects whose prostate-specific antigen (PSA) values were below 0.4 ng/ml, subjects had a history of increasing PSA levels prior to the trial. This increase continued during the trial both while on soy isoflavones and after treatment was discontinued. On average the rate of rise accelerated after soy isoflavones were discontinued, but that difference did not attain statistical significance. Genistein and daidzein were rapidly cleared from plasma and excreted in urine. Pharmacokinetic data for chronic dose administration were similar to single-dose administration for the isoflavones investigated except that we observed slightly longer circulation time for daidzein.

Two years of followup of the REDUCE study cohort demonstrated a low rate of new prostate cancer diagnoses in the former placebo and dutasteride treated groups. No new Gleason 8-10 cancers were detected.

The intravenous pharmacokinetic disposition of the novel, atypical anxiolytic CGS 9896 was studied in six cynomolgus monkeys. CGS 9896 was infused at dose levels of approximately 60, 120, and 240 micrograms/h/kg for a duration of 12 h, resulting in steady-state plasma concentrations averaging 38.4, 51.8, and 124 ng/ml, respectively. The average total systemic clearance was 35.3 ml/min/kg which was independent of dose and totally attributable to nonrenal pathways. The hepatic clearance was determined to be blood flow-rate dependent and the first-pass extraction calculated as approximately 84%. Both the apparent elimination rate constant and volume of distribution exhibited dose-dependent changes. Even though the plasma protein bound fraction was high (98.6%), no concentration dependency was observed. Furthermore, no concentration dependency was observed in the plasma/blood distribution ratio indicating the observed dose-related reduction in the volume of distribution may be attributable to nonlinear tissue uptake of CGS 9896.