Metabolism and toxicology studies

Important progress in terms of higher throughput in ADME/PK work was realized recently by wider use of liquid chromatography/mass spectrometry (LC/MS), which has now become a standard analytical tool [26]. Flow NMR spectroscopy has become a routine method to resolve and identify mixtures of compounds and has found applications in drug metabolism and toxicology studies [27]. 

Baden JM, Rice SA, Wharton RS, et al Metabolic and toxicologic studies with enflurane in Swiss/ICR mice. J Environ Pathol Toxicol 4(l) 293-303, 1980... 

Beta-emitters such as tritium (H-3) or carbon-14 (C-14) are the most commonly used radioisotopes in drug metabolism, agricultural metabolism, and toxicology studies. In HPLC, the radiochemical detector can be off-line or on-line. Off-line detection requires coupling the chromatograph to a fraction collector. The collected fractions are combined with a suitable liquid scintillation cock-tail and then counted by a liquid scintillation counter. This method allows for... 

Biosynthesis, degradation, metabolic and toxicologic studies involving... 

Roles of human cytochrome P450 enzymes involved in drug metabolism and toxicological studies 00YZ1347. 

Dosage Levels for Metabolism and Toxicology Studies. Administration of doses above those which saturate metabolic systems or the capacity-limited elimination rate in the test species can cause toxic effects which do not occur at lower dosage levels. This saturation can be the most sensitive indicator of overdosing and should be taken into consideration in choosing the Maximum Tolerated Dose (MTD) for toxicity studies. Toxicological effects generated in overdosed animals may simply be artifacts from which valid extrapolations to potential effects in humans cannot be made. 

Solvent suppression has been one of the rich areas in biological NMR research. The driving force comes from in vivo and in vitro proton NMR spectroscopy, protein structure determination, metabolic and toxicological studies of biofluids, and medical and functional magnetic resonance imaging. New methods could emerge from the following two fundamental techniques ... 

We postulate that the double13C -labeling technique presented in this chapter could be used to study adducts on large pieces of DNA and even follow the chemical details cellular metabolic processes in real time. The double 13C-labeling technique is currently being developed to solve problems in metabolism and toxicology. 

The naturally occurring mycotoxins, 125 and 126, produced mainly by fungi" and implicated in the variety of toxicoses in man and animals99 100, have been tritium labelled101 (equations 46 and 47) for use in toxicology metabolism and pharmacokinetic studies. Position 15 in verrucarol and position 16 in verrucarin A have been tritium-labelled, because they should not suffer from the loss of labelling protons during the... 

Cohen, S.M., Arnold, L.L., Eldan, M. et al. (2006) Methylated arsenicals the implications of metabolism and carcinogenicity studies in rodents to human risk assessment. Critical Reviews in Toxicology, 36(2), 99-133. 

Pesonen, M. and Andersson, T.B. (1997) Fish primary hepatocyte culture an important model for xenobiotic metabolism and toxicity studies, Aquatic Toxicology 37 (2-3), 253-267. 

It is necessary to pay attention to the fact that, during recent years, the bioinorganic properties of aluminum coordination compounds have become the objects of detailed study their general aspect [354], metabolism and toxicology [355,356], complex formation with nucleozides of di- and triphosphates and nucleo-zide-bound proteins [357], and x-ray analysis of biologically important complexes... 

Successful completion of the above experiments will characterize methods for use in evaluating a lead candidate in animal models. If a candidate is selected for further development, the method will need to be validated (3,4) for each matrix and for each species before being used to support definitive toxicology, drug metabolism, and pharmacokinetic studies. 

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