ARIMIDEX (ZD1033) - A SELECTIVE, POTENT INHIBITOR OF AROMATASE IN POSTMENOPAUSAL FEMALE VOLUNTEERS

Two multiple-dose studies were conducted in healthy post-menopausal fe male volunteers to investigate the pharmacokinetics and effects on end ocrinology of Arimidex (ZD1033). Volunteers in the first trial were do sed with 3 mg of ZD1033 daily over 10 days to assess the effects on en docrinology of ZD1033 and establish the pharmacokinetic profile. In th e second trial volunteers received 14 daily doses of either 0.5 or 1.0 mg of ZD1033 to assess the pharmacokinetics of ZD1033 and the effects of low doses of ZD1033 on serum oestradiol concentrations. Following multiple dosing a significant reduction in the concentration of serum oestradiol of approximately 80% of baseline was obtained with all thre e doses; no recovery in oestradiol was apparent for up to 144 h after the last dose. There was no overall difference in the level of oestrad iol suppression between the 0.5 or 1.0 mg doses of ZD1033. However, co mparison of the number of volunteers with oestradiol concentrations be low the limits of detection of the assay, 24 h after the last dose of ZD1033, suggested that 1.0 mg was the minimal dose required for maxima l suppression of oestradiol. No significant effect was recorded on ser um concentrations of gonadotrophins over the dosing period. Serum conc entrations of a range of adrenal steroids were not affected by adminis tration of ZD1033; furthermore, steroid response to standard adrenocor ticotrophic hormone (ACTH) challenge was unimpaired by ZD1033. Togethe r these data demonstrate the potency, tolerability and selectivity of ZD1033. The pharmacokinetic profile of ZD1033 supports its use as a on ce-daily treatment given orally.