A single-dose administration study of a new type of aromatase inactivator, exemestane, was performed in normal healthy postmenopausal Japanese women. The study was conducted to investigate the safety, effect on serum and urinary estrogen concentrations, and pharmacokinetics of exemestane at 25 or 50 mg. A crossover study using a single dose (25 mg) was also conducted in order to study the effect of meals on these parameters. Adverse events, in which a causal relationship with the study drug could not be excluded, were as follows: hot flushes (2/4), sleepiness (1/4), and glycogeusia (1/4), all of which were mild and transient. There were no clinically significant laboratory test or physical finding abnormalities with either dose, except for one patient in the 50 mg group who had an increase in levels of GPT, ALP and gamma-GTP. Maximal suppression of serum estrogen concentration (22-37% suppression) was achieved 3-4 days after single-dose administration of exemestane (25 mg or 50 mg), and almost no suppression was observed 2 weeks later. A significant decrease in the amount of urinary estrogen excretion occurred on day 4 and day 8 after exemestane administration. The level of urinary estrogen excretion almost returned to baseline levels in the 25 mg group and returned to 65% of baseline levels in the 50 mg group 2 weeks after drug administration. Both serum estrogen concentration and the amount of urinary estrogen excreted decreased in a similar fashion under both fasting and fed conditions, suggesting no effect of meals on the suppression of estrogen concentrations. Exemestane was adsorbed immediately after single-dose administration, and this was followed by a gradual decrease in serum concentrations in a multiphase pattern. An increase in Cmax and AUC0-tz values was observed after meals compared with those values obtained under fasting conditions, yet the increase was not statistically significant, suggesting that the increase was not clinically relevant. The results of this study verified the safety and the estrogen suppressive effects on serum and urinary concentrations of estrogen of a single dose of exemestane up to 50 mg. Furthermore, results suggest that the suppression of serum and urinary estrogen concentrations and pharmacokinetics of exemestane were not affected by food.