Preclinical trials pharmacodynamics

Before a drug may be tested on humans, it must first be tested on animals. Tests on humans are called clinical trials, and animal trials are often referred to as preclinical trials. Preclinical trials differ from the animal tests mentioned earlier in this chapter. The previously discussed animal tests help the drug discovery team determine and optimize the pharmacodynamic and pharmacokinetic behavior of a hit or lead. Preclinical trials, in contrast, are standardized, industrywide tests. The preclinical tests have technical names such as Segment II Reproductive Study in Rabbits or 6-Month Toxicity Study in Rats. The specific names suggest the exact nature of each study. Each trial seeks to answer predefined safety questions concerning a drug candidate. Preclinical trials do not address the therapeutic effectiveness of the drug candidate in any way. Preclinical trials examine exclusively safety issues. 

The trials described so far have commonly shown a lack of usefulness of NKi receptor antagonists in the treatment of pain. But we do not know whether the failure of the selected compounds is a matter of pharmacodynamics (e.g. poor penetration of the blood brain barrier) or a genuine discrepancy between animal and human pain pathophysiology (Urban and Fox, 2000). Hence, animal tests should carefully be chosen whether they are predictive or not, and it would be helpful if a wider range of conditions could be examined (Hill, 2000a). Therefore, new preclinical analysis methods should be developed for a more effective judgement of likely clinical outcomes. 

Drug Development Tests are performed on the lead compounds in test tubes (laboratory, in vitro) and on animals (in vivo) to check how they affect the biological systems. The tests, often called preclinical research activities, include toxicology, pharmacodynamics and pharmacokinetics, as well as optimization of drug delivery systems. Many iterations are carried out, and the leading compounds are modified and synthesized to improve their interactions with the targets, or to reduce the toxicity or improve pharmacokinetics performance. At the end of this process, an optimized compound is found and this becomes a potential drug ready for clinical trial... 

A DNA vaccine candidate that has successfully passed all preclinical hurdles needs to be tested clinically by a three-phased scheme as outlined in Chapter 4. As defined by a European Council directive, a clinical trial means ... any investigation in human subjects intended to discover or verify the clinical, pharmacological and/or other pharmacodynamic effects of. .. investigational medicinal product(s), and/or to identify any adverse reactions. .. and/or to study absorption, distribution. 

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