BIOAVAILABILITY STUDY OF MENOREST(R), A NEW ESTROGEN TRANSDERMAL DELIVERY SYSTEM, COMPARED WITH A TRANSDERMAL RESERVOIR SYSTEM

The aim of this study was to compare the bioavailability and plasma pr ofiles of estradiol and estrone after repeated applications of 2 types of estradiol transdermal systems: a new adhesive matrix system (Menor est(R)) compared with a reference membrane/reservoir system (Estraderm (R)) and to evaluate their short term safety. This was an open, random ised, crossover study, with 2 treatment periods of 10.5 days separated by a 10-day washout period and with a 1-week follow-up. Participants were studied at Institut Aster, Paris, and Association de Recherche Th erapeutique (ART), Lyon, France, and included 31 healthy post-menopaus al women, all volunteers aged between 49 and 67 years (mean 58 years). Each transdermal system was applied for three successive 3.5 day-wear periods (10.5 days) on the lower abdominal skin. Plasma estradiol and estrone concentrations were measured at steady-state, before and afte r the third application of each transdermal system at regular interval s over 106 hours. Cutaneous tolerance was assessed after each transder mal system removal. Although the extent of availability [area under th e plasma concentration-time curve (AUG) and average plasma concentrati on (C-av)] was similar with both transdermal systems, their pharmacoki netic profiles were different, with Menorest(R) producing less fluctua ting and more sustained plasma estradiol levels than the reference sys tem. The mean estradiol to estrone C-av ratio was similar with the 2 t ransdermal systems and in the physiological range of premenopausal sta tus. The incidence of adverse events was similar for both treatments, but a lower incidence of local erythema was observed with Menorest(R) (8.9%) than with the reference system(18.3%). In conclusion, during th e entire wear period, Menorest(R) produced more sustained plasma estra diol levels with less fluctuations (40 to 72 ng/L) than the reservoir/ membrane system(18 to 102 ng/L). Menorest(R) gave estradiol plasma lev els approximating the concentrations observed during the early to mid- follicular premenopausal stage, with a 2-fold lower incidence of eryth ema than with the reservoir/membrane system.