ABSTRACT
The rat is by far and large the most accepted rodent model for pre-clinical testing. With regard to predicting human PK, numerous prediction methodologies, incorporating both in vitro and pre-clinical in vivo data, have been developed in recent years, each with advantages and disadvantages. Even though the rat is not necessarily a worse predictor for human PK than for example the dog, it is recognised that this species has a higher oxidative metabolism than the human (Martignoni et al. 2006), which may lead to differences in metabolic profile that need to be adequately examined. From a safety testing perspective, retrospective data analysis has shown that when using a rodent model (rat) only, it will generally be predictive for 43% of human toxicities (Olson et al. 2000). Even though the mouse can be regarded as an alternative rodent species, its diminutive size can limit its use as a practical model for prolonged infusion studies, and it is considered a worse predictor of human toxicities (Olson et al. 2000).
