Dietary supplements of purified unconjugated isoflavones administered to humans in single doses exceeding normal dietary intake manyfold resulted in minimal clinical toxicity. Genistein and daidzein (free and total) were rapidly cleared from plasma and excreted in urine.

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.

No abstract

The maximum steady state flux, diffusion coefficients, and solubilities of five contraceptive steroids in homopolymers and copolymers of epsilon-caprolactone and DL-lactic acid were determined. The permeabilities of polymers of epsilon-caprolactone were comparable to silicone rubber and, by inference, are suitable for the construction of drug delivery devices. Poly(DL-lactic acid) was 10(4) times less permeable, although its permeability was significantly enhanced by additives.

No abstract

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.

No abstract

This is a report of the results of a placebo-controlled study in which the effects of the interaction between ethanol and marihuana on drug plasma concentrations, subjective ratings of intoxication, heart rate acceleration, and psychomotor performance were investigated. Six healthy, male, paid volunteers, moderate users of ethanol and marihuana, participated in the study. Ethanol (0.42 g/kg, 0.85 g/kg, or placebo) was administered over a 30-min interval. Fifteen minutes later the subjects smoked, in their customary manner, NIDA cigarettes containing 2.4% or 0.0004% (placebo) delta-9-tetrahydrocannabinol (THC). Each subject was tested in a single-blind, latin-square crossover design with the following six conditions: placebo ethanol/placebo marihuana; low dose ethanol/placebo marihuana; high dose ethanol/placebo marihuana; placebo ethanol/marihuana; low dose ethanol/marihuana; and high dose ethanol/marihuana. The variables measured in the study were: (a) subjective rating of ethanol and/or marihuana intoxication; (b) heart rate; (c) accuracy and latency of response in the Simulator Evaluation of Drug Impairment (SEDI) task; (d) blood ethanol concentration by gas chromatography; and (e) plasma concentration of THC by radioimmunoassay. The results indicate that the decrements due to ethanol in performance of skills necessary to drive an automobile were significantly enhanced by marihuana in an additive and perhaps synergistic manner. The administration of ethanol prior to marihuana smoking did not produce significant effects on the subjective rating of "high," heart rate acceleration, or THC plasma concentration.