A Järvinen1, A Bäckström, C Elfström, A Viitanen. 1. Department of Medicine, Helsinki University Central Hospital, P.O.B. 348, 00029, Hus, Finland. asko.jarvinen@hus.fi
Abstract
OBJECTIVES: To compare the absorption of estradiol from a transdermal gel and a novel matrix-type patch and to study the variability in absorption. METHODS:Twenty-four healthy postmenopausal women were treated in an open, randomized, cross-over study for 18 days with 1.0 mg estradiol daily as a transdermal gel and a transdermal patch releasing estradiol 50 microg/24 h without a wash-out between the periods. Venous blood samples for estradiol pharmacokinetics 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 estradiol time-concentration curve between the gel and the patch. However, trough estradiol concentration was significantly lower and fluctuation higher with the patch. Estradiol time-concentration curves on the 15th and 18th study days with the gel were almost superimposable. A significant difference was observed in peak estradiol levels, whereas area under the curve or trough estradiol level did not differ between the 15th and 18th study days with the gel. Inter- and intra-individual coefficients of variability were around 30% for peak estradiol level and area under the curve, except for the intra-individual coefficient of variability for area under the curve (21%) for the gel. The total coefficient of variability for area under the curve was 35% for the gel and 39% for the patch. CONCLUSIONS: A daily 1.0 mg estradiol dose as a transdermal gel seems to correspond with a matrix-type patch releasing 50 microg estradiol daily in the extent of estradiol absorption. High variability was associated with both treatments, and both the variabilities within and between the subjects were high with the gel. Wider than generally applied confidence limits should be applied for bioequivalence testing of transdermal estradiol formulations.
RCT Entities:
OBJECTIVES: To compare the absorption of estradiol from a transdermal gel and a novel matrix-type patch and to study the variability in absorption. METHODS: Twenty-four healthy postmenopausal women were treated in an open, randomized, cross-over study for 18 days with 1.0 mg estradiol daily as a transdermal gel and a transdermal patch releasing estradiol 50 microg/24 h without a wash-out between the periods. Venous blood samples for estradiol pharmacokinetics 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 estradiol time-concentration curve between the gel and the patch. However, trough estradiol concentration was significantly lower and fluctuation higher with the patch. Estradiol time-concentration curves on the 15th and 18th study days with the gel were almost superimposable. A significant difference was observed in peak estradiol levels, whereas area under the curve or trough estradiol level did not differ between the 15th and 18th study days with the gel. Inter- and intra-individual coefficients of variability were around 30% for peak estradiol level and area under the curve, except for the intra-individual coefficient of variability for area under the curve (21%) for the gel. The total coefficient of variability for area under the curve was 35% for the gel and 39% for the patch. CONCLUSIONS: A daily 1.0 mg estradiol dose as a transdermal gel seems to correspond with a matrix-type patch releasing 50 microg estradiol daily in the extent of estradiol absorption. High variability was associated with both treatments, and both the variabilities within and between the subjects were high with the gel. Wider than generally applied confidence limits should be applied for bioequivalence testing of transdermal estradiol formulations.