Metabolites, measurement

Davies JE, Peterson JC. 1997. Surveillance of occupational, accidental, and incidental exposure to organophosphate pesticides using urine alkyl phosphate and phenolic metabolite measurements. Aim NY Acad Sci 837 257-268. 

PBPK models have also been used to explain the rate of excretion of inhaled trichloroethylene and its major metabolites (Bogen 1988 Fisher et al. 1989, 1990, 1991 Ikeda et al. 1972 Ramsey and Anderson 1984 Sato et al. 1977). One model was based on the results of trichloroethylene inhalation studies using volunteers who inhaled 100 ppm trichloroethylene for 4 horns (Sato et al. 1977). The model used first-order kinetics to describe the major metabolic pathways for trichloroethylene in vessel-rich tissues (brain, liver, kidney), low perfused muscle tissue, and poorly perfused fat tissue and assumed that the compartments were at equilibrium. A value of 104 L/hour for whole-body metabolic clearance of trichloroethylene was predicted. Another PBPK model was developed to fit human metabolism data to urinary metabolites measured in chronically exposed workers (Bogen 1988). This model assumed that pulmonary uptake is continuous, so that the alveolar concentration is in equilibrium with that in the blood and all tissue compartments, and was an expansion of a model developed to predict the behavior of styrene (another volatile organic compound) in four tissue groups (Ramsey and Andersen 1984). 

In a study in which pregnant rats received a single 6-hour exposure to 1,000 ppm -hcxane on gestation day 12 or 20 (Bus et al. 1979), w-hexanc was rapidly and extensively metabolized to methyl- -butyl ketone (2-hexanone) and 2,5-hexanedione. 2-Hexanone and 2,5-hexanedione (the only metabolites measured) were... 

Ideal for studying the dose-response relationship for QT interval prolongation taking into account all the pharmacological properties of a compound The dog model is one of the most widely used anesthetized rabbits (especially female rabbits) have also been proposed for high sensitivity It provides complementary information with respect to in vitro tests (activity of metabolites, measurement of plasma drug concentrations, calculation of the volume of distribution) Possibility to induce experimental TdP... 

For the quantitative description of the metabolic state of a cell, and likewise which is of particular interest within this review as input for metabolic models, experimental information about the level of metabolites is pivotal. Over the last decades, a variety of experimental methods for metabolite quantification have been developed, each with specific scopes and limits. While some methods aim at an exact quantification of single metabolites, other methods aim to capture relative levels of as many metabolites as possible. However, before providing an overview about the different methods for metabolite measurements, it is essential to recall that the time scales of metabolism are very fast Accordingly, for invasive methods samples have to be taken quickly and metabolism has to be stopped, usually by quick-freezing, for example, in liquid nitrogen. Subsequently, all further processing has to be performed in a way that prevents enzymatic reactions to proceed, either by separating enzymes and metabolites or by suspension in a nonpolar solvent. 

Prior to the genomics era, most metabolite measurements were performed in targeted approaches such as spectrophotometric assays or HPLC with UV detection. Today, these methods are still the best choice for the analysis of small numbers of metabolites. In spectrophotometric assays, metabolites are first... 

In the first year, the maximum concentrations of sulfoxide and sulfone in soil, seed potatoes, and foliage were approximately 2, 2, and 6 times, respectively, the concentrations of those metabolites measured in the second and third year treatments. These results demonstrated that enhanced microbial degradation of relatively minor insecticidal compounds in the soil can significantly affect insecticide levels in the plant (when these degradation products are the major insecticidal component accumulated). As the sulfoxide and the sulfone metabolites are the major toxicants in the foliage of potato plants grown in disulfoton-treated soil, this reduction in toxicant residues overtime can be expected to reduce insecticide efficacy. 

Some studies showed already that the levels of phthalate substitute s metabolites measured in human s urine are usually lower when compared to DEHP metabolites (Table 7) [105, 135]. However, such comparison should be carefully addressed since it was shown through rats exposure to such plasticizers that a considerable portion (about 50%) of the orally dosed DINP is excreted via the feces while it is known that DEHP is mainly extracted in humans via urine [105, 141]. 

This section deals with the question of whether there are quantitatively detectable and interpretable correlations between the dose of an administered drug, or the concentration of a drug and its metabolites measured in the blood or plasma (blood or plasma level), and the therapeutic action or side effects observed. Investigations relating to questions of this type are called PK PD (pharmacokinetic pharmacodynamic) studies. The PK PD analysis is a bidirectional approach pharmacokinetics represent what the body does with a drug, and pharmacodynamics describes what a drug does to the body. The PK PD analyses are key elements of early drug development, and PK PD trials are able to answer specific disease-related efficacy and safety questions. 

Metabolite measurements have been used to assess health for decades, and so metabolomics is not a revolutionary approach to medicine, toxicity or nutri-... 

Whether these dififerenees also apply to other metabolites sueh as 6-MMPR has not been systematieally analyzed. Generally, thiopurine metabolite measurements show large intra- and inter-individual variation (79,110,112,123,124). Targeted therapeutic ranges for 6-TGN levels under 6-MP therapy are described between 225 and 500 pmol/ 8 X 10 RBC. For 6-MMPR, levels lower than 5700pmol/8 x 10 RBC are aimed at. 

In Europe, quantitative schemes exist for most common metabolites measured in biochemical genetics laboratories (see Table 1.2.1). 

Biocides are known to be tracked into the homes after a certain outdoor application (Lewis and Nishioka, 1999 Nishioka et al., 2001). Furthermore transport routes, that is, transfer from the workplace to the home (para-occupational or take-home exposure) may be relevant. Household dust concentrations of azino-phosmethyl, chlorpyrifos, parathion and phosmet were significantly lower in reference homes when compared with farmer/farmworker homes (Simcox et al., 1995). Dialkyl phosphate metabolites measured in children s urine were elevated for agrarian children compared with children whose parents did not work in agriculture (Fenske et al., 2000). 

Parentheses indicate yields based on spectroscopic analysis, metabolite measurements, or consumption of starting materials. 

Szulc A, Galinska B, Tarasow E, Dzienis W, Kubas B, et al. 2005. The effect of risperidone on metabolite measures in the frontal lobe, temporal lobe, and thalamus in schizophrenic patients. A proton magnetic resonance spectroscopy (lh mrs). Pharmacopsychiatry 38 214-219. 

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