Preclinical safety pharmacolog

Burchiel, S.W. and Weaver, J.L., Uses of Flow cytometry in preclinical safety pharmacology and toxicology, in Flow Cytometry for Biotechnology, Sklar, L.A., Ed., Oxford University Press, New York, NY, 2005, 275-290. 

Anderson, H., Spliid, H., Larsen, S. and Dali, V (2000). Statistical analysis of time to event data from preclinical safety pharmacology studies. Tox. Methods 10 111-125. 

Various reasons why preclinical safety pharmacology tests may not accurately predict human adverse effects include the following ... 

Some biotechnologically derived pharmaceuticals will cross-react with species that can be evaluated toxicologically, while others cross-react only with nonhuman primates such as the chimpanzee, a protected species. In this case, a well-designed safety, or Phase 0 study at doses higher than the proposed clinical dose may provide valuable safety information. However, a lack of cross-reactivity with any nonhuman species does not necessarily make preclinical safety evaluation impossible, not does it limit toxicity testing to species in which the protein lacks relevant pharmacological activity. Some alternative possibilities are summarized in Table 12.9. 

Zbinden, G. (1966). The significance of pharmacologic screening tests in the preclinical safety evaluation of new drugs. J. New Drugs 6 1-7. 

Part 11), preclinical data on the pharmacodynamics, pharmacokinetics, safety pharmacology and toxicology of the material (Part 111), and any clinical data already generated (Part IV). 

Figure 2.1 The evolution of the drug-likeness concept. Drug-likeness evolved from empirical rules such as Lipinski s rule of 5 through more sophisticated data mining algorithms into utilization of preclinical profiling and safety pharmacology data [3].

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