Pharmacology and toxicity data

Items 1-3 and 9 and 10 are self-explanatory and will not be discussed further. Items 4-6, and 9 on Investigational Plan, Investigator s Brochure, and Protocols and human experience are covered in Chapter 6, and Pharmacology and Toxicity data are discussed in Chapter 5. We will concentrate our discussion on Item 7. 

Chemical, biological, pharmacological and toxicity data Protein-Protein interactions, pathways, biomarkers etc... 

Aryl acetic Acids - Of several aryl acetic acids described in the last report, no significant developments have been noted regarding ibufenac and namoxyrate. Detailed pharmacology and toxicity data on... 

For products in a new pharmacological class where there is no human experience, the pharmacology and pharmacodynamics data will be scrutinized closely by assessors to look for indicators of possible toxicity. Any application should contain a thorough description of the following ... 

Such factors may change not only the kinetics of an enzyme reaction but also the whole pattern of metabolism, thereby altering the bioavailability, pharmacokinetics, pharmacological activity, or toxicity of a xenobiotic. Species differences in response to xenobiotics must be considered during the extrapolation of pharmacological and toxicological data from experiments in animals to humans. The primary factors in these differences probably are the rate and pattern of drug and xenobiotic metabolism in the various species. 

Many laboratory animal models have been used to describe the toxicity and pharmacology of chloroform. By far, the most commonly used laboratory animal species are the rat and mouse models. Generally, the pharmacokinetic and toxicokinetic data gathered from rats and mice compare favorably with the limited information available from human studies. PBPK models have been developed using pharmacokinetic and toxicokinetic data for use in risk assessment work for the human. The models are discussed in depth in Section 2.3.5. As mentioned previously, male mice have a sex-related tendency to develop severe renal disease when exposed to chloroform, particularly by the inhalation and oral exposure routes. This effect appears to be species-related as well, since experiments in rabbits and guinea pigs found no sex-related differences in renal toxicity. 

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