Absorption and bioavailability of oestradiol from a gel, a patch and a tablet

To compare oestradiol and oestrone concentrations and bioavailability after a single dose and at a steady state during oral oestradiol valerate, transdermal oestradiol gel and transdermal oestradiol patch treatments.

Two open, randomised, cross-over studies were conducted. In the first study, 12 healthy postmenopausal women received 1.5 mg oestradiol as a transdermal gel or a 2 mg oestradiol valerate tablet daily for 14 days. In the second study, 15 postmenopausal women were treated for 18 days with 1.5 mg oestradiol gel or a transdermal patch releasing oestradiol 50 microg/24 h (replaced every 72 h). Venous blood samples for serum oestradiol and oestrone measurements with RIA were taken until 24 or 72 h after the first and last doses.

The tablet and the transdermal gel yielded similar serum oestradiol profiles with a peak concentration 4-5 h after administration. The patch resulted in relatively stable oestradiol levels during the mid third of the wearing time whereas much lower levels were observed in the beginning and towards the end. There was no difference in the fluctuation between the peak and trough oestradiol levels between the gel (56 or 67%) and the tablet (54%) while the fluctuation was greater with the patch (89%). The bioavailability of oestradiol from the gel was 61% as compared with the tablet and 109% as compared with the patch. The gel was not bioequivalent with the tablet or the patch.

The doses used of the transdermal gel and the patch roughly corresponded to each other with regard to the amount of oestradiol absorbed whereas the bioavailability from the tablet was significantly higher than from the gel. The lack of bioequivalence, the different serum oestradiol profiles and the large intersubject variability suggest that individual dose adjustments may be needed when changing administration form.