Descriptive studies, metabolic profiling

The development phases shifts from a predictive, prospective nature trying to influence drug design to a descriptive study of the complete metabolic profile of the candidate drug. Work done in this phase has significant impact on both the safety plan as well as the clinical pharmacology plan. Additional characterization of the metabolism of the drug after all the metabolic pathways... 

Although most toxicological data reviewed in this profile have been obtained from studies in which PCB mixtures were used, Section 3.4.3 (Metabolism) in particular, contains descriptions of studies in which individual PCB congeners were used. This supplemental information is considered necessary since most of the current knowledge regarding biotransformation of chlorinated biphenyls in experimental animals has been derived from such studies. Table 4-2 lists the lUPAC number of the congeners and the corresponding chlorine substitution. 

The value of obtaining multiple datasets from various biofluid samples and tissues of the same animals collected at different time points has been demonstrated. This procedure has been termed integrated metabonomics [2] and can be used to describe the changes in metabolic chemistry in different body compartments affected by exposure to toxic drugs. An illustration of the types of information that can be obtained is shown in Figure 13.3-6, from an NMR spectroscopic study of the acute toxicity of a-naphthylisothiocyanate, a model liver toxin [53]. Such timed profiles in multiple compartments are characteristic of particular types and mechanisms of pathology and can be used to give a more complete description of the biochemical consequences than can be obtained from one fluid or tissue alone [54]. 

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