PLASMA ESTRADIOL CONCENTRATIONS AND PHARMACOKINETICS FOLLOWING TRANSDERMAL APPLICATION OF MENOREST(R)-50 OR SYSTEN(R) (EVOREL(R))-50

Objectives: In order to compare the pharmacokinetics of two transderma l estrogen replacement therapy (ERT) systems designed to release 50 mu g 17 beta-estradiol/day, two studies were performed in healthy postme nopausal volunteers. Methods: Both studies had a cross-over design and incorporated a 1-week wash-out period between treatments. In the firs t study, Menorest(R) 50 and Systen(R) 50 (Evorel(R) 50) were compared over four days of application in 30 women. In the second, 13 women wor e each of the two systems for a total of 12 days each (three patches e ach for 4 days), and comparison was made during the third patch period (steady state, between days 8 and 12). Plasma 17 beta-estradiol level s were assayed using specific direct radioimmunoassays, and pharmacoki netic parameters were calculated by standard methods. All the samples of the first study were re-analysed using a different radioimmunoassay and the results of both assays were compared. Results: In both studie s, plasma 17 beta-estradiol levels rose at a comparable rate and reach ed similar peak levels with each of the two formulations. Levels then remained relatively constant throughout both evaluation periods with M enorest 50, but began to decline after 12 hours in the first study and after 30 h under steady state conditions in the second study with Sys ten(R) 50. The difference between the two products was statistically s ignificant in both studies. Analysis of pharmacokinetic parameters con firmed the greater bioavailability of Menorest(R) 50. In addition, 17 beta-estradiol levels remained within the suggested therapeutic ranges for relief of acute symptoms and protection against osteoporosis for longer periods of rime with Menorest(R) 50 than with Systen(R) 50. Con clusion: Since the acute efficacy, long-term protective effects, side effects and risks associated with ERT may depend on critical threshold plasma levels, much attention should be paid to the pharmacokinetic p rofiles of different formulations. The comparison of these two differe nt radioimmunoassays demonstrates the comparability of their results. (C) 1997 Elsevier Science Ireland Ltd.