Pharmacokinetics of the transdermal reservoir membrane system delivering beta-estradiol: in vitro/in vivo-correlation.
OBJECTIVE
The aim of our study was to investigate the high fluctuations of Estradiol (E2) plasma levels transdermally delivered in postmenopausal women by a commercially available membrane controlled reservoir system (MCRS).


METHODS
The transdermal E2 flux either out of a complete MCRS or across its membrane out of defined ethanol water mixtures was determined, as well as E2 plasma profiles in 6 postmenopausal women produced by a MCRS.


RESULTS
The transdermal in vitro E2 flux rate out of a complete MCRS, claimed to deliver 25 microg/day, increased steadily, reaching a maximum value of 2.06 +/- 0.58 microg/h at 30 to 40 hours and decreased to a rate of about 0.5 microg/h from 60 to 90 hours. No statistically significant differences between plasma profiles calculated from the in vitro investigation and derived from a clinical study could be identified. The E2 flux in defined ethanol/water mixtures across MCRS-membrane, adhesive and skin layer increased with increasing ethanol concentrations up to a maximum of 227 +/- 34 ng/cm2/h at an ethanol concentration of 62.5% (V/V) and decreased with further increase in the volume fraction of ethanol.


CONCLUSIONS
In vitro as well as in vivo investigations showed high fluctuation of E2 plasma profiles in postmenopausal women produced by the MCRS. These fluctuations are caused by a non-constant input rate of E2 which may be due to changing ethanol concentrations in the reservoir of the MCRS.
Rohr
U D
UD
Department of Pharmaceutics and Biopharmacy, Philipps-University, Marburg, Germany.
Altenburger
R
R
Kissel
T
T
D000279:Administration, Cutaneous; D004958:Estradiol / Q000008:administration & dosage / Q000493:pharmacokinetics*; D015914:Estrogen Replacement Therapy; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008875:Middle Aged; D017698:Postmenopause; D012867:Skin / Q000378:metabolism
D004958:Estradiol