Preclinical drug development animal models

An autoimmune response is rarely detected during preclinical drug development because of the lack of good predictive animal models for the human immune system. Owing to their low incidence and idiosyncratic nature, autoimmune diseases quite often appear as a serious issue only after product launch [2,22]. 

Preclinical drug development involves understanding of dosage, formulation, and route of administration, typically in animal models, so that safe and effective doses for human administration can be estimated. The drug development phase extends from prechnical assessment through clinical testing. 

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. 

The evaluation of undesired ocular drug side-effects has become an impor-tant issue in preclinical drug development and possible cataractogenic potentials are key issues in this respect (Hockwin and Wegener, 1987). A number of animal cataract models has been established in rodents, their suitability for toxicological research, however, varies considerably. 

Undertake preclinical studies (Preclinical Development) this involves many different important steps, of which the most critical is safety evaluation of the efficacious drug candidate in animal models. Before introduction of any new drug in humans it must be shown to be safe in animals. 

The growing understanding of off-target deleterious mitochondrial drug effects has prompted development of preclinical models and screens to detect it and hence ways to circumvent it. Early preclinical vigilance, combined with animal models that resolve liver lesions previously only detected in the clinic [82], will surely reduce late-stage attrition and incidence of side effects that are caused by mitochondrial impairment. 

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. 

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