Bioequivalence study of an oral contraceptive containing ethinylestradiol/drospirenone/levomefolate calcium relative to ethinylestradiol/drospirenone and to levomefolate calcium alone

Hartmut Blode; Christine Klipping; Frank Richard; Dietmar Trummer; Beate Rohde; Konstanze Diefenbach

doi:10.1016/j.contraception.2011.05.015

Bioequivalence study of an oral contraceptive containing ethinylestradiol/drospirenone/levomefolate calcium relative to ethinylestradiol/drospirenone and to levomefolate calcium alone

Contraception. 2012 Feb;85(2):177-84. doi: 10.1016/j.contraception.2011.05.015. Epub 2011 Jul 19.

Authors

Hartmut Blode¹, Christine Klipping, Frank Richard, Dietmar Trummer, Beate Rohde, Konstanze Diefenbach

Affiliation

¹ Bayer HealthCare Pharmaceuticals, D-13342 Berlin, Germany. [email protected]

PMID: 22067789
DOI: 10.1016/j.contraception.2011.05.015

Abstract

Background: A new tablet formulation containing 0.02 mg ethinylestradiol/3 mg drospirenone/0.451 mg levomefolate calcium (calcium salt containing 0.416 mg L-5-methyltetrahydrofolate) was assessed for bioequivalence compared to the approved oral contraceptive (OC) tablet containing identical amounts of ethinylestradiol and drospirenone and to a tablet containing 0.451 mg levomefolate calcium.

Study design: Forty-four subjects received in an intraindividual crossover design single doses of the new tablet formulation or the established ethinylestradiol/drospirenone tablet or the levomefolate calcium tablet.

Results: Bioequivalence was demonstrated for ethinylestradiol, drospirenone and L-5-methyltetrahydrofolate (active moiety of levomefolate calcium) between the investigated tablet formulations. The geometric mean ratios of the AUC((0-tlast)) and C(max) values for all three compounds and their 90% confidence intervals were well within the 80%-125% range generally accepted to demonstrate bioequivalence.

Conclusion: The rate and extent of absorption of ethinylestradiol and drospirenone were not affected by the concomitant administration of levomefolate calcium and vice versa.

Publication types

Comparative Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

MeSH terms

Adolescent
Adult
Androstenes / administration & dosage
Androstenes / adverse effects
Androstenes / pharmacokinetics*
Calcium / administration & dosage
Calcium / adverse effects
Calcium / pharmacokinetics*
Contraceptives, Oral, Combined / administration & dosage
Contraceptives, Oral, Combined / adverse effects
Contraceptives, Oral, Combined / pharmacokinetics*
Cross-Over Studies
Estrogens / administration & dosage
Estrogens / adverse effects
Estrogens / pharmacokinetics*
Ethinyl Estradiol / administration & dosage
Ethinyl Estradiol / adverse effects
Ethinyl Estradiol / pharmacokinetics*
Female
Glutamates / administration & dosage
Glutamates / adverse effects
Glutamates / pharmacokinetics*
Humans
Mineralocorticoid Receptor Antagonists / administration & dosage
Mineralocorticoid Receptor Antagonists / adverse effects
Mineralocorticoid Receptor Antagonists / pharmacokinetics*
Therapeutic Equivalency
Young Adult

Substances

Androstenes
Contraceptives, Oral, Combined
Estrogens
Glutamates
Mineralocorticoid Receptor Antagonists
drospirenone and ethinyl estradiol combination
Ethinyl Estradiol
levomefolate calcium
Calcium