Anastrozole – A New Generation in Aromatase Inhibition: Clinical Pharmacology

Use of the aromatase inhibitor aminoglutethimide is limited by its lack of selectivity for aromatase and its toxicity. Newer agents are more selective, but do not always offer improved inhibition of aromatase. Indirect comparison of their activity in inhibiting aromatase and suppressing plasma oestrogens indicates that aminoglutethimide, rogletimide, formestane, and fadrozole inhibited aromatase activity by 74–91%, with reported falls in oestradiol level of 58–76%. In contrast, the new-generation oral once-daily aromatase inhibitors anastrozole (Arimidex®) and letrozole were of a similar activity, inhibiting aromatase activity by over 96%, with a concomitant fall in oestradiol and oestrone levels of at least 80%. Anastrozole at the recommended clinical dose of 1 mg daily also suppressed oestrone sulphate levels by 93.5%; activity with anastrozole 10 mg daily was not statistically significantly different. The new generation of aromatase inhibitors, as typified by anastrozole, thus offers effective and convenient aromatase inhibition which correlates well with decreases in the levels of plasma oestrogens.