Metabolism and distribution

Turkall, R.M. (1979) Gold sodium thiomalate selected aspects of metabolism and distribution. Ph. D. Thesis, University of Ohio. 

A. Rescigno, Mathematical foundations of linear kinetics. In Pharmacokinetics Mathematical and Statistical Approaches to Metabolism and Distribution of Chemicals and Drugs. (J. Eisenfeld and M. Witten, Eds.), North-Holland, Amsterdam, 1988. 

Compounds such as LSD or the beta-carbolines do not possess a primary amino group, are not rapidly metabolized in comparison to, for example, tryptamine, and enter the brain readily certain substituent groups can alter this situation. Members of the phenylalkylamine and indolealkylamine families of hallucinogens can produce similar effects in animals but may be capable of producing distinctive effects in man. As yet, there is no satisfactory and comprehensive structure-activity relationship that encompasses both major classes of compounds. This may be due in part to unique metabolic and distributional characteristics associated with the individual ring systems. 

Kyerematen GA, Owens GF, Chattopadhyay B, deBethizy JD, Vesell ES (1988b) Sexual dimorphism of nicotine metabolism and distribution in the rat. Studies in vivo and in vitro. Drug Metab Dispos 16 823-828... 

L B. Although all of the compounds are nitrogen mustards and have the same basic mechanism of action, differences in the toxicity profile, duration of action, metabolism, and distribution within the body... 

Lautier J., J.L. Chanal, and A. DeUion (1986). Comparative hydrolipidemic effects of clofibric acid and itanoxone on the metabolism and distribution of lipids in the crab Pachygraspus marmoratus (Decopoda, Brachyura). Comparative Biochemistry and Physiology C 85 269-274. 

Because distribution studies have monitored total radioactivity, our understanding of the distribution of intact di(2-ethylhexyl) phthalate is limited. Chu et al. (1978) studied the metabolism and distribution of mono(2-ethylhexyl) phthalate in rats after oral dosing and found that the intestine contained the highest tissues levels after 24 h. The liver, heart, lung and muscle each contained approximately half the level in the intestine. They also reported that 80% of the I C-dose of mono(2-ethylhexyl) phthalate was eliminated 24 h after oral administration, 72% in the urine and 8% in the faeces. Twenty minutes after the administration of an intravenous dose of [ C]mono(2-ethyl-hexyl) phthalate, Chu et al. (1978) found comparable levels in the liver, kidney and bladder, with other organs containing approximately 10-25% of the level of the liver. 

The importance of the physicochemical characteristics of compounds has already been alluded to in the previous two chapters. Thus, lipophilicity is a factor of major importance for the absorption, distribution, metabolism, and excretion of foreign compounds. Lipophilic compounds are more readily absorbed, metabolized, and distributed, but more poorly excreted, than hydrophilic compounds. 

The onset of symptoms depends on the particular organophosphorus compound, but is usually relatively rapid, occurring within a few minutes to a few hours, and the symptoms may last for several days. This depends on the metabolism and distribution of the particular compound and factors such as lipophilicity. Some of the organophosphorus insecticides such as malathion, for example (chap. 5, Fig. 12), are metabolized in mammals mainly by hydrolysis to polar metabolites, which are readily excreted, whereas in the insect, oxidative metabolism occurs, which produces the cholinesterase inhibitor. Metabolic differences between the target and nontarget species are exploited to maximize the selective toxicity. Consequently, malathion has a low toxicity to mammals such as the rat in which the LD50 is about 10 g kg-1. 

Mathews. J.M.. Troxler. P.S. Jeffcoat. A.R. (1990) Metabolism and distribution of bromodichloromethane in rats after single and multiple oral doses. J. Toxicol, environ. Health, 30, 15-22... 

Takeda, Y. (1966). Studies of the metabolism and distribution of fibrinogen in healthy men with autologous 125-I-labeled fibrinogen./ Clin. Invest. 45, 103-111. 

In metabolism and distribution studies, armodafinil s primary metabolic pathway is via a non-CYP-related amide hydrolysis. As a result, concomitant medications having CYP-interactions are not likely to have deleterious effects (or drug-drug interactions) on the pharmacokinetic profile of armodafinil. The details of the pharmacokinetics of armodafinil are listed in Table 1. 

Route of Exposure. As discussed below, the route of uptake may have a significant influence on the metabolism and distribution of a material. Differences in route of exposure may influence the amount of material absorbed and its subsequent fate. These differences may be reflected in variation in the nature and magnitude of the toxic effect. 

Transport and Transformation of Chemicals A Perspective. - Transport Processes in Air. - Solubility, Partition Coefficients, Volatility, and Evaporation Rates. - Adsorption Processes in Soil. - Sedimentation Processes in the Sea. - Chemical and Photo Oxidatioa - Atmospheric Photochemistry. -Photochemistry at Surfaces and Interphases. -Microbial Metabolism. - Plant Uptake, Transport and Metabolism. - Metabolism and Distribution by Aquatic Animals. - Laboratory Microecosystems. - Reaction Types in the Environment. -Subject Index. 

Matis, J., An introduction to stochastic compartmental models in pharmacokinetics, Pharmacokinetics-Mathematical and Statistical Approaches in Metabolism and Distribution of Chemicals and Drugs, edited by A. Pecile and A. Rescigno, Plenum Press, New York, 1988, pp. 113-128. 

ADI Acceptable daily intake the amount of a specific food additive or contaminant (e.g., pesticide) thought to be the maximum level that should be consumed on a daily basis. ADI values are normally determined by experts of the WHO/FAO Codex Alimentarius Committee ADME Absorption, distribution, metabolism, and distribution ADR Adverse drug reaction... 

In drug development, it is important to know that the compound has reached its intended target as well as to understand the absorption, excretion, bioavailability, metabolism, and distribution (e.g., the pharmacodynamics and pharmacokinetics) of the compound. Direct monitoring of human in vivo drug and metabolite concentrations in the target organs or in adverse event-related organs, such as the brain, liver, or heart, is often needed to understand the therapeutic impact, potential adverse events, or other effects. 

Validation of the model. The Farris et al. model simulations were compared to an extensive set of data collected by the authors on the metabolism and distribution of an orally dosed bolus of radiolabeled methylmercury in male Sprague-Dawley rats. In a distribution study, tissue samples were collected on days 3, 7, 14, 21, 28, 35, 42, 49, 56, 63, 70, 77, 84, 91, and 98 post-dosing. In a metabolism study with the same dosing regimen, whole body counts and 24-hour feces and urine samples were collected daily for 15 days post-dosing, and then twice weekly. 

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