Novel ethinyl estradiol-beta-cyclodextrin clathrate formulation does not influence the relative bioavailability of ethinyl estradiol or coadministered drospirenone.
BACKGROUND
A new combined oral contraceptive formulation has been developed consisting of a beta-cyclodextrin (betadex) clathrate formulation of ethinyl estradiol in combination with drospirenone (EE-betadex clathrate/drsp). In this novel EE-betadex clathrate/drsp preparation, betadex serves as an inert complexing agent to enhance stability and shelf-life. The study was conducted to investigate the relative bioavailability and pharmacokinetic parameters of EE and drsp after oral administration of EE-betadex clathrate/drsp.


METHODS
This was an open-label, randomized, single-dose, three-period, three-treatment, crossover study conducted in 18 healthy postmenopausal women aged 45-75 years. The women received single oral doses of 40 mcg EE/6 mg drsp formulated as EE-betadex clathrate/drsp or EE/drsp (EE as a free steroid) tablets, or as a microcrystalline suspension on three separate occasions. Serum samples were collected for pharmacokinetic analyses.


RESULTS
The relative bioavailability of EE and drsp after EE-betadex clathrate/drsp tablet administration was comparable with that achieved with the EE/drsp tablet (107% and 101%, respectively). In addition, the inclusion of EE in a betadex clathrate does not affect the pharmacokinetics of either EE or drsp. There were no safety concerns with any of the medications.


CONCLUSIONS
The betadex clathrate formulation of EE, when combined with DRSP, does not affect the pharmacokinetics and relative bioavailability of either EE or drsp.
Blode
Hartmut
H
Clinical Pharmacokinetics, Bayer Schering Pharma AG, Müllerstrasse 172-178, 13342 Berlin, Germany. hartmut.blode@bayerhealthcare.com
Schürmann
Rolf
R
Benda
Norbert
N
D000368:Aged; D000736:Androstenes / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical; D003277:Contraceptives, Oral, Combined / Q000008:administration & dosage / Q000493:pharmacokinetics*; D003280:Contraceptives, Oral, Synthetic / Q000008:administration & dosage / Q000493:pharmacokinetics; D018592:Cross-Over Studies; D004997:Ethinyl Estradiol / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D008875:Middle Aged; D000451:Mineralocorticoid Receptor Antagonists / Q000008:administration & dosage / Q000493:pharmacokinetics*; D011310:Preservatives, Pharmaceutical / Q000008:administration & dosage / Q000493:pharmacokinetics; D013535:Suspensions / Q000737:chemistry / Q000493:pharmacokinetics; D013607:Tablets / Q000737:chemistry / Q000493:pharmacokinetics; D047392:beta-Cyclodextrins / Q000008:administration & dosage / Q000493:pharmacokinetics*
D000736:Androstenes; D003277:Contraceptives, Oral, Combined; D003280:Contraceptives, Oral, Synthetic; D000451:Mineralocorticoid Receptor Antagonists; D011310:Preservatives, Pharmaceutical; D013535:Suspensions; D013607:Tablets; D047392:beta-Cyclodextrins; D004997:Ethinyl Estradiol; C031215:betadex; C035144:drospirenone