Pharmacokinetic comparison between Conpremin (Premarin) and a generic preparation of conjugated estrogens.
OBJECTIVE
To determine the relative bioavailability of the estrogenic components of a generic brand of conjugated estrogens marketed in Chile in comparison to that of Conpremin (Premarin in the United States).


METHODS
A randomized cross-over study was conducted on 16 healthy postmenopausal women receiving single oral doses of either two Conpremin 0.625-mg tablets or two 0.625-mg tablets of the generic brand, with a 14-day wash-out interval between doses. A gas chromatography tandem mass spectrometry assay was used to determine estrogen components.


RESULTS
The peak plasma concentrations of unconjugated and total estrone and equilin, unconjugated 17 beta-dihydroequilin and 17 beta-estradiol were higher and occurred earlier with the generic conjugated estrogens than with Conpremin. The 90% confidence limits for both variables lay outside the accepted bioequivalence limits of 80-125%. Additionally, no measurable plasma concentration of unconjugated delta 8,9-dehydroestrone or 17 beta-delta 8,9-dehydroestradiol was seen after administration of the generic conjugated estrogens.


CONCLUSIONS
These pharmacokinetic results indicate that the generic tablets do not have the modified-release characteristics of Conpremin tablets. In addition, the absence of delta 8,9-dehydroestrone and 17 beta-delta 8,9-dehydroestradiol in the plasma indicates that the generic form is not compositionally equivalent to Conpremin.
Arteaga
E
E
Department of Endocrinology, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile.
Villaseca
P
P
D000328:Adult; D001682:Biological Availability; D002677:Chile; D018592:Cross-Over Studies; D016568:Drugs, Generic / Q000493:pharmacokinetics*; D004857:Equilin / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D004958:Estradiol / Q000097:blood / Q000493:pharmacokinetics; D004966:Estrogens, Conjugated (USP) / Q000493:pharmacokinetics*; D004970:Estrone / Q000097:blood / Q000493:pharmacokinetics; D005260:Female; D006801:Humans; D008875:Middle Aged; D017698:Postmenopause; D013810:Therapeutic Equivalency; D014481:United States
D016568:Drugs, Generic; D004966:Estrogens, Conjugated (USP); D004857:Equilin; D004970:Estrone; D004958:Estradiol; C014482:dihydroequilin