Data Supporting Technique

Clearly, to be able to apply this approach in projects at an early stage, a validation is necessary that convinces the teams that this data will be useful. To this end, dose, C ax (maximum plasma concentration), and C ,i (minimum plasma concentration, at 12 h time point) data from a number of AZ CD compounds (22 compounds in total, comprising 4 acids, 6 bases, 11 neutrals, and 1 zwitterion) that have entered phase I clinical trials, usually across a number of dose levels, were collated. Human dose predictions (eD2M values) for this compound data set were also undertaken, using the models and inputs described above, while in vitro clearance was described by CLm, data determined in human hepatocytes. All clinically utilized human doses were then normalized in two ways. 

1) Normalized observed dose = Clinical dose (mg) Ci2h(eD2M)/Ci2h (observed) 

Median values for each normalized dose set per compound were then used for comparison with eD2M values obtained. The first approach shows the accuracy of the eD2M prediction. The second gives an indication as to how accurate the eD2M Cmax value is compared to that observed. Both approaches allow a comparison even where the clinical doses used are very different from those predicted by the model for one or more study-related reasons. 

1 Matching eD2M Doses with Normalized Observed Clinical Doses 

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The simplest of all of the homoaromatics is the homocyclopropenium cation [2], This species was first invoked as an unusually stable intermediate by Applequist and Roberts (1956) to explain the reactions of methylene cyclobutenes with electrophiles. Since that time a wealth of studies has provided data supporting the special stability of the monohomocyclo-propenium cation (Story and Clark, 1972 Paquette, 1978). The parent cation and several simple derivatives have been examined by a variety of techniques including the convincing, direct H and 13C NMR observation... 

These three case studies indicate that the MSG technique is indeed successful in showing strong responses over background in areas of base metal, Cu-Ni and porphyry Cu mineralization. All data support the contention that gaseous metais do exist in soil gas and can be used as a practical tool for mineral exploration in areas covered both with residual and exotic overburden. 

Harmonization activities focus on reducing and simplifying the types of studies that the pharmaceutical industries need to carry out in order to register a medical product in another country, protocols to be followed when performing these studies, techniques used to validate supporting data, and techniques used to perform risk assessment. 

In the evaluation of acquired NMR data, one must consider whether the quality of the spectra and other accompanying information are sufficient for identification, or whether the data should only be regarded as support to an identification made by other techniques (Figure 1). One must consider whether all resonances of the chemical were revealed (S/N occurrence and significance of overlapping resonances of other chemicals), whether the resonance patterns in the sample and reference spectra match, and whether they are correctly interpreted, whether the sample conditions were comparable to those of the reference sample, whether the reference data are of adequate quality, and in the case of interpretation, how the related data supported the identification <43>. 

M. J. A. Berry and G. Linoff Data Mining Techniques For Marketing, Sales, and Customer Support,Wiley, New York, 1997. 

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