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 Cmax (+ 306 nmol l-1; 95% CI on the difference: 117, 496). The AUC and Cmax 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 17beta-oestradiol during co-administration with ketoconazole is unlikely to be clinically significant.