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Chapter – 6 Biological evaluation of newly.....
6.3.1 TOXICITY RISK ASSESSMENT
Recent high-profile drug withdrawals increase the pressure on
regulators and the pharmaceutical industry to improve preclinical safety
testing. Understanding mechanisms of drug toxicity is an essential step
toward improving drug safety testing by providing the basis for mechanismbased
risk assessments. Nonetheless, despite several decades of research
on mechanisms of drug-induced toxicity and the application of various new
technologies to preclinical safety assessment, the overall impact on preclinical
safety testing has been modest. Assessing the risk of exposing humans to
new drug candidates still depends on preclinical testing in animals, which in
many, but not all cases, predicts outcomes in humans accurately. The
following offers a perspective on the challenges and opportunities facing
efforts to improve preclinical safety testing and outlines gaps and needs that
must be addressed. A case is built for focusing solutions on defined problems
within the current safety testing paradigm rather than imposing wholesale
change. Targets for application of new technologies are available now.
Improving drug safety testing will depend on improving the application of
mechanism-based risk assessment but will also require improving public and
private collaborations in order to focus research regarding the mechanism of
drug-induced toxicity on the most important problems.
Before doing the toxicity prediction we ran a set of toxic compounds
and a set of presumably non-toxic compounds through the prediction. The
data below shows the results obtained by predicting all available structures of
four subsets of the database. E.g. all structures known to be mutagenic were
run through the mutagenicity assessment. 86 % of these structures where
found to bear a high or medium risk of being mutagenic. As a control set
served a collection of traded drugs of which the mutagenicity risk assessment
revealed only 12 % of potentially harmful compounds.
Results of given substance, which obtain from one of those kind of
procedures are mentioned.
Department of Chemistry, Saurashtra University, Rajkot – 360 005 340