The effect of ketoconazole and diltiazem on oestrogen metabolism in postmenopausal women after single dose oestradiol treatment

Aims  The effect of the CYP3A4 inhibitors ketoconazole and diltiazem on the pharmacokinetics of oestrone was studied in six healthy postmenopausal women after treatment with a single oral dose of oestradiol.

Methods  Plasma oestrone concentrations were measured following the administration of 1) oestradiol, 2) oestradiol and ketoconazole and 3) oestradiol and diltiazem.

Results  Treatment with ketoconazole increased the AUC of oestrone (+ 4029 nmol l⁻¹ h; 95% CI on the difference: 1588, 6471) and its C_max (+ 306 nmol l⁻¹; 95% CI on the difference: 117, 496). The AUC and C_max of oestrone tended to increase on treatment with diltiazem although this did not reach the level of statistical significance.

Conclusions  The small increase in the plasma concentrations of oestrone formed from 17β‐oestradiol during co‐administration with ketoconazole is unlikely to be clinically significant.

DOI: 10.1046/j.1365-2125.2003.01885.x

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