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The effect of anastrozole on the pharmacokinetics of tamoxifen in post-menopausal women with early breast cancer.Dowsett, Mitch; Tobias, J S; Howell, Anthony; Blackman, G M; Welch, H; King, N; Ponzone, R; Von Euler, M; Baum, M; Academic Department of Biochemistry, Royal Marsden Hospital, London, UK. (1999-01)Thirty-four post-menopausal women with early breast cancer who had received 20 mg tamoxifen once daily as adjuvant therapy for at least 10 weeks participated in a randomized, double-blind, parallel-group, multicentre trial. The primary aim of the trial was to determine the effect of anastrozole upon tamoxifen pharmacokinetics, with secondary aims of assessing the tolerability of the two drugs in combination and whether or not tamoxifen had any effect upon the oestradiol suppression seen with anastrozole. Patients were randomized to receive either 1 mg anastrozole (16 patients) or matching placebo (18 patients) once daily on a double-blind basis for 28 days. No significant difference (P = 0.919) was observed in serum tamoxifen concentrations between the anastrozole and placebo groups during the trial. The serum concentration of oestradiol was significantly suppressed (P < 0.0001) in patients co-administered anastrozole compared with placebo in the presence of tamoxifen, confirming that anastrozole remained an effective suppressant of oestradiol in the presence of tamoxifen. The combination of tamoxifen and anastrozole was well tolerated, with very little difference in side-effects reported between anastrozole and placebo. In conclusion, the results of this study confirm that anastrozole does not affect the pharmacokinetics of tamoxifen when the two drugs are given in combination to post-menopausal women with early breast cancer. In addition, the oestradiol suppressant effects of anastrozole appear unaffected by tamoxifen.