Abstract

Background: The choice of an appropriate reference product is still a problem within the European Union. When no direct comparisons between originator products in different countries are available, registration authorities are sometimes only prepared to grant registration for a generic product on the basis of a comparison with the originator product in the respective country. The aim of the investigation was therefore to evaluate the bioequivalence of reference products from different origins in two different bioequivalence trials with the same test drug. Methods: Two separate bioequivalence trials were performed involving the oral administration of one test and two reference products containing 500 mg metformin. Both studies had a randomized, open, single-dose, three-period crossover design and were carried out in 24 healthy volunteers. The reference products in the first trial were Glucophage mite (Germany) and Diabex (Australia). In the second trial the reference drugs were Glucophage mite (France) and Glucophage mite (Switzerland). The results of each trial were analyzed regarding the bioequivalence of the respective reference drugs. Findings: The reference drugs in each of both trials were bioequivalent: the 90% confidence intervals for both AUC_{0 ? tlast} and C_max were entirely within the acceptance range for bioequivalence trials (0.80 ? 1.25 for both parameters). Interpretation: In the case of metformin, the reference products available in the countries examined were very similar. This retrospective analysis involving two studies, therefore, confirmed bioequivalence between these reference products.

Author Details

Authors

• V. Vlahov
• U. Thyroff-Friesinger
• R. Koytchev
• N. Bakracheva
• E. Gatchev

Departments

• ¹ Chair of Clinical Pharmacology, Multidisciplinary Hospital for Active Treatment Queen Giovanna, Sofia, Bulgaria,
• ² HEXAL Pharmaforschung GmbH, Holzkirchen, and
• ³ CCDRD AG, Neuenhagen, Germany

Address

R. Koytchev CCDRD AG Fontanestra
Email: [email protected]

Citation