Biomarkers metabolic process

Lead hematotoxicity is not only a toxic endpoint of Pb exposure in humans and animals but also provides biomarkers of Pb exposures via early toxic effects on the heme and erythropoietic pyrimidine biosynthesis pathways. Although heme biosynthesis is largely considered here in terms of heme production for utilization in hemoglobin, it is a critical cofactor for diverse metabolic processes, including in the cytochromes and for the 1-hydroxylase enzyme system responsible for generating the hormonal form... 

Isoprene (CsHg) is an abundant endogenous hydrocarbon contained in exhaled breath (typically at a level of hundreds of ppbv) and is considered to be linked to a number of metabolic processes in the human body, and in particular as a biomarker for cholesterol... 

A key consideration regarding the practical aspects of biomarkers is the pharmacokinetics of the chemical. The measure usually referred to is the half-life, which reflects both the affinity of the chemical for the biologic matrix and the efficiency of metabolic or elimination processes. Knowledge of half-life is important for several reasons, including its use in determining sampling time (Bernard 1995). For instance, chemicals with short half-lives (a few days or even a few hours)—including cotinine, phthalates, volatile... 

For the sake of simplicity, simple monophasic pharmacokinetics (one compartment and one half-life) was assumed in the above example and in many other examples in this report. In real life, most chemicals express biphasic or polyphasic pharmacokinetics (several compartments and several half-lives). Squeezing a polyphasic pharmacokinetic behavior into a one-compartment model by assuming a single half-life may lead to negligible errors for some chemicals and serious misinterpretation of biomarker concentrations for others. The same can be said about nonlinear processes, such as metabolic induction, inhibition, and saturation. A good way to check the accuracy of a simple pharmacokinetic model is to verify its performance by comparing with a physiologically based pharmacokinetic (PBPK) model that may encompass the mentioned factors. 

Following absorption, NMP is uniformly distributed throughout all major organs in the rat with a volume of distribution (about 0.71 kg ) that approximates total body water. In both the rat and man, NMP is eliminated primarily by metabolism to other compounds via a saturable process only about 2% of the absorbed NMP is excreted unchanged. The major metabolite is 5-hydroxy-NMP (50-70%) with lesser amounts of N-methylsuccinimde, 2-hy-droxy-N-methylsuccinimide, and possibly other unidentified metabolites. The half-life of NMP in plasma is 4h. Studies with radiolabeled NMP indicate the most of the radiolabel is excreted in the urine ( 95%), with lesser amounts in the feces ( 5%) and expired air ( 2%). Ongoing studies are investigating the use of 5-hydroxy-NMP as a urinary biomarker for human exposures to NMP. 

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