Intoxication toxicokinetics

Boereboom FT, van Dijk A, van Zoonen P, et al. 1998. Nonaccidental endosulfan intoxication A case report with toxicokinetic calculations and tissue concentrations. Clin Toxicol 36(4) 345-352. 

Methods of detection, metabolism, and pathophysiology of the brevetoxins, PbTx-2 and PbTx-3, are summarized. Infrared spectroscopy and innovative chromatographic techniques were examined as methods for detection and structural analysis. Toxicokinetic and metabolic studies for in vivo and in vitro systems demonstrated hepatic metabolism and biliary excretion. An in vivo model of brevetoxin intoxication was developed in conscious tethered rats. Intravenous administration of toxin resulted in a precipitous decrease in body temperature and respiratory rate, as well as signs suggesting central nervous system involvement. A polyclonal antiserum against the brevetoxin polyether backbone was prepared a radioimmunoassay was developed with a sub-nanogram detection limit. This antiserum, when administered prophylactically, protected rats against the toxic effects of brevetoxin. 

Of particular interest in brevetoxin research are the diagnosis of intoxication and identification of brevetoxins and their metabolites in biological fluids. We are investigating the distribution and fate of radiolabeled PbTx-3 in rats. Three model systems were used to study the toxicokinetics and metabolism of PbTx-3 1) rats injected intravenously with a bolus dose of toxin, 2) isolated rat livers perfused with toxin, and 3) isolated rat hepatocytes exposed to the toxin in vitro. 

What the body does to the drugs which enter the system may be referred to as pharmacokinetics. During a drug overdose and subsequent intoxication, the various parameters for pharmacokinetics are altered, and these will include changes in elimination half-lives, protein binding, saturation kinetics and excretion. These deviations from the normal pharmacokinetics may be referred to as toxicokinetics. 

Exposure. The major data insufficiency with respect to biomarkers is the lack of quantitative factors that can be measured either in-life or postmortem, and that are uniquely indicative of white phosphorus poisoning. This deficiency is related to the lack of definitive information regarding white phosphorus toxicokinetics. Because little is known about the fate of white phosphorus in the body, there are no substance-quantity or substance-presence tests that are currently available that indicate white phosphorus intoxication. 

Our studies of the oximes focused on mechanism and SAR of recovery neuromuscular transmission after intoxication with OPC, pharmacokinetics of these oximes and changes which have been seen after such intoxications, changes in toxicokinetics of OPC after treatment with reactivators of ChE. The results of... 

The changes in pharmacokinetics of oximes after intoxication with OPC have shown that monitoring of their plasma levels when administering to man will improve the therapy. The same in OPC toxicokinetics after treatment with oximes can explain the reinhibition of ChE, which was pointed is some cases. 

Toxicokinetic studies of nerve agents deal with the in vivo absorption, distribution, and elimination of these agents as a function of animal species, route of administration, dose, and time after administration. Such studies are essential to provide a quantitative basis for the toxicology of nerve agents and, in combination with toxicodynamic studies, are the starting point for development of causal treatment of intoxications with these agents. Toxicodynamic studies of nerve agents have been... 

The competitive replacement Tl /K creates an interesting toxicokinetic factor in terms of thallium elimination, namely direct active excretion into the intestinal lumen. In contrast to other toxic heavy metals, fecal elimination of thallium is the predominant route of excretion. In addition to thallium possibly binding in the gastrointestinal tract in cases of acute intoxication (cf. Section 22.6.2), reabsorption may occur by the enterohepatic and enterosystemic circulations, thereby prolonging the biological half-life. In fact, half-lives of between 3 and... 

Lead toxicokinetics serves two critical roles in the delineation of lead toxicity. First, it provides the kinetic imderpinnings for expressions of lead intoxication in humans and other species. The rate of Pb entry into, and deposition within, tissues and cellular organelles is a prerequisite for toxic expressions with differing Pb exposiures. 

The rat is a generally accepted model for toxicokinetic studies. Maisonneuve et al (1993) do not provide a rationale for choosing this rodent as an animal model for sulfur mustard intoxication. The authors only studied the intravenous (iv) toxicokinetics. 

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