Pharmacokinetic comparison between Conpremin® (Premarin®) and a generic preparation of conjugated estrogens

Abstract

Objectives 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 17β-dihydroequilin and 17β-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 Δ^8–9-dehydroestrone or 17 β-Δ^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 Δ^8–9-dehydroestrone and 17β-Δ^8–9-dehydroestradiol in the plasma indicates that the generic form is not compositionally equivalent to Conpremin.

Key Words:

• Premarin®
• Δ^8–9-Dehydroestrone