Drug concentration effect relationship of estradiol from two matrix transdermal delivery systems: Menorest (R) and Climara (R)

Objectives: To relate the pharmacokinetics of estradiol to pharmacological effects. Methods: Drug concentration effect relationship of estradiol from two matrix transdermal delivery systems, Menorest(R) and Climara(R), was st udied in a single centre, open. randomised, comparative crossover study. Th e trial consisted of two treatment periods, 14 days for each patch separate d by a 4-week washout period. Blood hormone levels were followed during the second week of each treatment. Estradiol levels during treatments were rel ated to three concentration levels previously proposed as efficacy ol safet y limits. The effect of treatment on FSH-levels was examined and the relati onship between the levels of estradiol and FSH was described using an inhib itory sigmoidal I-max model. Estrone levels and estradiol/estrone before an d Juring treatment were followed. Results: The C-average of FSH during trea tment was 38% lower than baseline plasma levels. Estradiol had an inhibitor y effect on FSH with an I-max of 0.68 and an IC50 of 19 pg/ml. The fi actio n of lime above the minimum concentration for therapeutic effect and the to lerability limit did not differ between the two treatments, whereas the fra ction of time above the suggested threshold for osteoporosis prophylaxis wa s significantly larger for Menorest(R) than for Climara(R) (P < 0.05). The low baseline estradiol/estrone ratios increased towards pre-menopausal leve ls during treatment. Conclusions: The drug concentration effect relationshi p of estradiol may be of use in evaluation of the effects of prophylactic e strogen therapy and to facilitate comparisons between different forms of es trogen treatments. (C) 2000 Elsevier Science Ireland Ltd. All rights reserv ed.