الكاتب: Multiple References

To obtain marketing approval, generic formulations must demonstrate bioequivalence to the marketed pioneer product in every target animal species included on the pioneer product label. This policy necessitates that generic drug sponsors submit multiple bioequivalence investigations, each employing approximately 20 animals. Inherent in this requirement is the assumption that product bioequivalence cannot be extrapolated across target animal species. It is widely recognized that serum drug concentrations can vary across animal species because of interspecies differences in clearance, volume of distribution, and in gastrointestinal (GI) physiology (Kalarli, 1995; Riviere et al., 1997). Parenteral drug absorption may likewise vary as a result of differences in the physico-chemical properties of the injection site (Baggot & Brown, 1998). Furthermore, interspecies differences are known to occur in metabolic endproducts, protein binding and enterohepatic recycling (Riond et al., 1990; Davies & Morris, 1993; Short, 1993). Nevertheless, while two animal species may exhibit dissimilar serum concentration/time pro®les, they may show similar effects of product formulation on product drug absorption characteristics.