Effects of the aromatase inhibitor anastrozole on serum oestrogens in Japanese and Caucasian women.
OBJECTIVE
Substantial differences in plasma oestrogen disposition have been reported between Japanese and Caucasian women, but there are currently few data available on the relative endocrinological effects of aromatase inhibitors in these two groups. Hence, the effects of the nonsteroidal aromatase inhibitor anastrozole on serum oestrogen concentrations were compared in 24 healthy postmenopausal Japanese women and 24 healthy postmenopausal Caucasian women.


METHODS
Anastrozole, 1 mg/day, was given once daily for 16 days. Serum oestradiol and oestrone sulphate levels were measured on three consecutive days beginning 2 days before the first dose, and on a further three consecutive days beginning on the penultimate day of dosing. Trough concentrations of anastrozole (measured 24 h after dosing) were also determined during the same periods.


RESULTS
There were no substantial differences in plasma oestrogen concentrations between the Japanese and Caucasian women at baseline. On average, anastrozole suppressed serum oestradiol and oestrone sulphate levels by approximately 87% and 93%, respectively, for both Japanese and Caucasian women, and minimum plasma anastrozole concentrations at steady-state (anastrozole C(min)) were also similar in both groups. Statistical analysis of serum oestradiol and serum oestrone sulphate levels, and plasma anastrozole C(min) showed that there were no statistically significant differences between the Japanese and Caucasian women.


CONCLUSIONS
Neither the pharmacodynamic effects of anastrozole on serum oestrogens nor the pharmacokinetics of anastrozole differ between postmenopausal Japanese and Caucasian women. Hence, these findings suggest that the therapeutic benefits of anastrozole in Caucasians will be predictive of the drug's effect in Japanese women and support the use of anastrozole in postmenopausal Japanese women with breast cancer.
Department of Academic Biochemistry, Royal Marsden Hospital, London, UK. mitch@icr.ac.uk
M
M
Dowsett
K
K
Donaldson
M
M
Tsuboi
J
J
Wong
R
R
Yates
D000368:Aged; D000077384:Anastrozole; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology*; D047072:Aromatase Inhibitors; D044466:Asian People; D001943:Breast Neoplasms / Q000453:epidemiology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004958:Estradiol / Q000097:blood; D004967:Estrogens / Q000097:blood*; D004970:Estrone / Q000031:analogs & derivatives / Q000097:blood; D005260:Female; D006801:Humans; D007564:Japan / Q000208:ethnology; D008875:Middle Aged; D009570:Nitriles / Q000494:pharmacology*; D014230:Triazoles / Q000494:pharmacology*; D044465:White People
D018931:Antineoplastic Agents, Hormonal; D047072:Aromatase Inhibitors; D004791:Enzyme Inhibitors; D004967:Estrogens; D009570:Nitriles; D014230:Triazoles; D004970:Estrone; D000077384:Anastrozole; D004958:Estradiol; C017296:estrone sulfate