Pharmacokinetic considerations action resulting

While rodents probably serve as the most utilized safety testing animal model for human health protection, there are limitations that are important to recognize. Beyond fundamental xenogenic differences with humans that can result in species differences in pharmacokinetics and actions of certain chemicals, rodent and human immune development does not proceed on an identical timeline. Landreth (2002) and Landreth and Dodson (2005) have shown that some events that occur gestationally in humans happen postnatally in rodents. This may be a consideration if limited exposure windows are utilized or if the maternally transferred exposure in rodents could not simulate the appropriate human fetal exposure. Therefore, knowledge of drug metabolism and the... 

The objectives of preclinical testing to support development of new medicines are to detect and characterize unwanted actions, whether inherently toxic or secondary to pharmacological effects of the substance and its pharmacokinetics, to exclude predicted harmful effects, and as far as possible to reveal other, potentially valuable actions. All this must be done in such a way that the results are both scientifically and administratively useful, as GLP and GMP considerations are essential, and the duration and costs of the of the studies are minimized. In this way the necessary resources of scientists, experimental animals, and laboratory facilities can be minimized in order to make the development of products to treat sick patients as efficient, humane, speedy, and economical as possible. 

The rate and extent to which the active moiety is absorbed from a pharmaceutical dosage form and becomes available at the site(s) of action. Reliable measurements of drug concentrations at the site(s) of action are usually not possible. The substance in the general circulation, however, is considered to be in equilibrium with the substance at the site(s) of action. Bioavailability can be therefore defined as the rate and extent to which the active pharmaceutical ingredient or active moiety is absorbed from a pharmaceutical dosage form and becomes available in the general circulation. Based on pharmacokinetic and clinical considerations it is generally accepted that in the same subject an essentially similar plasma concentration time course will result in an essentially similar concentration time course at the site(s) of action. 

---