Pharmacological properties animal models

During preclinical assessment of an enantiometric mixture, it may be important to determine to which of these three classes it belongs. The pharmacological and toxicological properties of the individual isomers should be characterized. The pharmacokinetic profile of each isomer should be characterized in animal models with regard to disposition and interconversion. It is not at all unusual for each enantiomer to have a completely different pharmacokinetic behavior. 

Canton T, Bohme GA, Boireau A, et al (2001) RPR 119990, a novel alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid antagonist synthesis, pharmacological properties, and activity in an animal model of amyotrophic lateral sclerosis. J Pharmacol Exp Ther 299 314-322... 

In the hope of developing either a more effective agent or one with fewer adverse effects, medicinal chemists have synthesized a number of new compounds. Preclinical animal model studies are used to select potentially useful drugs, using a profile of pharmacological properties reflecting differential blockade of dopamine, as well as other neurotransmitter systems (e.g., 5-HT). This research has led to the development of several new classes, as noted earlier in this chapter. 

Biopharmaceuticals represent a broad but discrete class of large molecular weight therapeutic entities that are characterized by their specific pharmacological activities and distinctive pharmacokinetics. The selection of an appropriate animal model is dependent on a combination of PD and PK factors. As described in this chapter, it is essential to understand the relationship of the basic pharmacology of a biopharmaceutical (signaling, receptor presence, binding properties, etc.) and the associated PK properties to that expected in humans, in order to select animal species that will have the most predictive value in safety assessments. 

The components of preclinical drug development can be divided into four general areas that include (1) in vitro studies to define a new agent s pharmacologic properties (2) drug supply and manufacturing, (3) drug formulation, and, finally, (4) in vivo studies in animal models to provide an initial proof of therapeutic principle and demonstrate the potential for clinical efficacy. 

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