Drug resistance toxicological studies

Toxicology studies must be performed in at least two animal species. If the toxicity profile of the compound is acceptable, then it joins the hit or lead list of compounds to proceed. The metabolism of the compound must be understood and pharmacokinetic studies must be performed in small and large animals. Efficacy studies must be performed in relevant animal models, especially in chimpanzees when more than one candidate is identified and a choice has to be made before proceeding to studies in humans. The ultimate preclinical steps include various studies testing drug combinations in vitro and in vivo, selection of resistant viruses, viral fitness, pyrophosphorolysis, and others. 

Whereas the GST were studied originally because of their involvement in mercapturic acid biosynthesis, these enzymes are also currently of interest to researchers working in fields other than toxicology. Some of the research areas in which GST are of importance include tumor markers, inherited cancer susceptibility, drug resistance, biotechnology, and clinical biochemistry. 

HDO is a reliable and accurate method for non-invasive blood pressure measurement. The use of this technology allows for blood pressure and cardiovascular information to be more frequently assessed and thus included into safety pharmacology and toxicology studies. Early detection of impaired vascular resistance can be added as a key parameter in the detectirm and assessment of heart and kidney disease as well as for use in metabolic research such as diabetes. Visualisation and analysis of single pulse waves, pulse pressure, the opening behaviour of the artery and in particular also pulse transit time might open new dimensions in the overall cardiovascular and metabolic evaluation of drugs for use in patients. 

Introduction - Research on antineoplastic agents follows an orderly sequence. Drugs which exhibit antitumor activity in animals bearing transplanted neoplasms or cytotoxicity in cell cultures are considered for further study. These chemicals are examined with respect to toxicology, effects upon resistant tumors, and biochemical mechanism of action. 

---