Drug concentration effect relationship of estradiol from two matrix transdermal delivery systems: Menorest and Climara.
OBJECTIVE
To relate the pharmacokinetics of estradiol to pharmacological effects.


METHODS
Drug concentration effect relationship of estradiol from two matrix transdermal delivery systems, Menorest and Climara, was studied in a single centre, open, randomised, comparative crossover study. The trial consisted of two treatment periods, 14 days for each patch separated by a 4-week washout period. Blood hormone levels were followed during the second week of each treatment. Estradiol levels during treatments were related to three concentration levels previously proposed as efficacy or safety limits. The effect of treatment on FSH-levels was examined and the relationship between the levels of estradiol and FSH was described using an inhibitory sigmoidal I(max) model. Estrone levels and estradiol/estrone before and during treatment were followed.


RESULTS
The C(average) of FSH during treatment was 38% lower than baseline plasma levels. Estradiol had an inhibitory effect on FSH with an I(max) of 0.68 and an IC(50) of 19 pg/ml. The fraction of time above the minimum concentration for therapeutic effect and the tolerability limit did not differ between the two treatments, whereas the fraction of time above the suggested threshold for osteoporosis prophylaxis was significantly larger for Menorest than for Climara (P<0.05). The low baseline estradiol/estrone ratios increased towards pre-menopausal levels during treatment.


CONCLUSIONS
The drug concentration effect relationship of estradiol may be of use in evaluation of the effects of prophylactic estrogen therapy and to facilitate comparisons between different forms of estrogen treatments.
Department of Clinical Pharmacology, University Hospital of Lund, S-221 85, Lund, Sweden. tomas.andersson@klinfarm.lu.se
T L
TL
Andersson
B
B
Stehle
B
B
Davidsson
P
P
Höglund
D000279:Administration, Cutaneous; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems; D004958:Estradiol / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D015914:Estrogen Replacement Therapy; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D006801:Humans; D008875:Middle Aged; D015663:Osteoporosis, Postmenopausal / Q000517:prevention & control
D004958:Estradiol; D005640:Follicle Stimulating Hormone