Comparative absorption and variability in absorption of estradiol from a transdermal gel and a novel matrix-type transdermal patch

Objectives: To compare the absorption of estradiol from a transdermal gel a nd a novel matrix-type patch and to study the variability in absorption. Me thods: Twenty-four healthy postmenopausal women were treated in an open, ra ndomized cross-over study for 18 days with 1.0 mg estradiol daily as a tran sdermal gel and a transdermal patch releasing estradiol 50 mug/24 h without a wash-out between the periods. Venous blood samples for estradiol pharmac okinetics were taken on the 15th and 18th study days of the gel period and during the 15th-18th study days during the patch period. Results: There was no significant difference in peak estradiol level or area under the estrad iol time-concentration curve between the gel and the patch. However, trough estradiol concentration was significantly lon er and fluctuation higher. w ith the patch. Estradiol time-concentration curves on the 15th and 18th stu dy days with the gel were almost superimposable, A significant. difference was observed in peak estradiol levels? whereas area under the curve or trou gh estradiol level did not differ between the 15th and 18th study days with the gel. Inter- and intra-individual coefficients of variability were arou nd 30% for peak estradiol level and area under the curve. except for the in tra-individual coefficient of variability for area under the curve (21%) fo r the gel. The total coefficient of variability for area under the curve wa s 35% for the gel and 39% for the patch. Conclusions: A daily 1.0 my estrad iol dose as a transdermal gel seems to correspond with a matrix-type patch releasing 50 mug estradiol daily in the extent of estradiol absorption. Hig h variability was associated with both treatments, and both the variabiliti es within and between the subjects were high with the gel. Wider than gener ally applied confidence limits should be applied for bioequivalence testing of transdermal estradiol formulations. (C) 2001 Elsevier Science Ireland L td. All rights reserved.