Biomarker safety

The purpose of this chapter is to describe the analytical methods that are available for detecting, measuring, and/or monitoring methyl parathion, its metabolites, and other biomarkers of exposure and effect to methyl parathion. The intent is not to provide an exhaustive list of analytical methods. Rather, the intention is to identify well-established methods that are used as the standard methods of analysis. Many of the analytical methods used for environmental samples are the methods approved by federal agencies and organizations such as EPA and the National Institute for Occupational Safety and Health (NIOSH). Other methods presented in this chapter are those that are approved by groups such as the Association of Official Analytical Chemists (AOAC) and the American Public Health Association (APHA). Additionally, analytical methods are included that modify previously used methods to obtain lower detection limits and/or to improve accuracy and precision. 

Walker, C.H. (1998c). The use of biomarkers to measure the interactive effects of chemicals. Ecotoxicology and Environmental Safety 40, 65-70. 

In a Phase la study in healthy volunteers, ARRY-438162 was well tolerated up to 20mg/kg q.d. oral dose. There was a dose proportional increase in plasma concentration and decrease in the production of IL-1 ft, TNFa, IL-6 and pERK in the ex-vivo-stimulated whole blood from drug treated volunteers. Array has initiated a Phase lb study of ARRY-438162 in combination with methotrexate in rheumatoid arthritis patients with the goals of assessing safety, tolerability, pharmacokinetics (PK), biomarkers and initial signs of efficacy. 

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