Toxicology kinetics

Kinetic toxicology, also known as metabolic or pharmacologic toxicology, involves toxicants that are transported and metabolized in the body. Such substances are called systemic poisons and they are studied under the discipline of systemic toxicology. Systemic poisons may cross cell membranes (see Chapter 3) and act on receptors such as cell membranes, bodies in the cells, and specific enzyme systems. The effect is dose responsive, and it is terminated by processes that may include metabolic conversion of the toxicant to a metabolic product, chemical binding, storage, and excretion from the organism. 

Define nonkinetic toxicology and how it relates to corrosive substances. What is kinetic toxicology and how does it relate to systemic poisons ... 

Potency/biological activity Pharmacokinetic profile Absorption time from tissue vs. IV Circulating half-life Distribution and elimination kinetics Toxicological profile Immunogenic potential Patient population characteristics Disease state Pathophysiology Age... 

An example is poly(bis(p-carboxyphenoxy)propane) (PCPP) which has been prepared as a copolymer with various levels of sebacic anhydride (SA). Injection molded samples of poly (anhydride) / dmg mixtures display 2ero-order kinetics in both polymer erosion and dmg release. Degradation of these polymers simply releases the dicarboxyhc acid monomers (54). Preliminary toxicological evaluations showed that the polymers and degradation products had acceptable biocompatibiUty and did not exhibit cytotoxicity or mutagenicity (55). 

B. V. Robinson and co-workers, PUP, M Critical Keview of the Kinetics and Toxicology of Polyvinylpyrrolidone (Povidone), Lewis, Chelsea, Mich., 1990. 

Gustafsson, K., Bjork, M., and Burreau, S. et al. (1999). Bioaccumulation kinetics of bromi-nated flame retardants (polybrominated diphenyl ethers) in blue mussels (Mytilus edu-lis). Environmental Toxicology and Chemistry 18, 1218-1224. 

Monteiro, L.R. and Furness, R.W (2001). Kinetics, dose-response, excretion and toxicity of methyl mercury in free living Cory s shearwater chicks. Environmental Toxicology and Chemistry 20, 1816-1824. 

A drug product, therefore, must satisfy stability criteria chemically, toxicologically, therapeutically, and physically. Basic principles in pharmaceutical kinetics can often be applied to anticipate and quantify the... 

Vol. 21 Reilctance Spectroscopy. By Wesley Wm.Wendlandt and Harry G. Hecht Vol. 22 The Analytical Toxicology of Industrial Inorganic Poisons. By the late Morris B. Jacobs Vol. 23 The Formation and Properties of Precipitates. By Alan G.Walton Vol. 24 Kinetics in Analytical Chemistry. By Harry B. Mark, Jr. and Garry A. Rechnitz Vol. 25 Atomic Absorption Spectroscopy. Second Edition. By Morris Slavin Vol. 26 Characterization of Organometallic Compounds (in two parts). Edited by Minoru Tsutsui Vol. 27 Rock and Mineral Analysis. Second Edition. By Wesley M. Johnson and John A. Maxwell Vol. 28 The Analytical Chemistry of Nitrogen and Its Compounds (in two parts). Edited by C. A. Streuli and Philip R.Averell... 

Freeman, R.A. 1979. Ecological kinetics of silver in an alpine lake ecosystem. Pages 342-358 in L.L. Marking and R.A. Kimerle (eds.). Aquatic Toxicology. Proceedings of the Second Annual Symposium on Aquatic Toxicology. ASTM special technical publication 667. Amer. Soc. Test. Mater., Philadelphia, PA 19103. 

Relationship between pharmacological or toxicological effects and the kinetics of the test compound. 

Hutzler, J.M., Steenwyk, R.C., Smith, E.B., Walker, G.S. and Wienkers, L.C. (2004) Mechanism-based inactivation of cytochrome P450 2D6 by l-[(2-ethyl-4-methyl-1 H-imidazol-5-yl) methyl]-4-[4-(trifluoromethyl)-2-pyridinyl]piperazine kinetic characterization and evidence for apoprotein adduction. Chemical Research in Toxicology, 17 (2), 174—184. 

Dose selection for exploratory studies requires knowledge of the pharmacology, toxicology metabolism and kinetics in animals and man. This is discussed in detail in Chapter 4. 

Gillespie WR, Cheung LL, Kim HJ, et al. 1990. Application of system analysis to toxicology Characterization of carbon tetrachloride oral absorption kinetics. In Gentry TR, Henry CJ, eds. Principles of route-to- route, extrapolations for risk assessment. Elsevier Science Publishing Company. 

Guideline Section 2 specifies that only mammalian species are to be used in the studies to be described. The rat is noted as being generally the most practical choice. A second species is traditionally required, and the rabbit is the preferred choice. Other species or a second rodent species may be used on a case-by-case basis. Note 5 associated with Section 2 points out that a single species can be sufficient if kinetic, pharmacological, and toxicological data show it to be a relevant model for the human. However such a complete set of data are very rarely available prior to the time such studies are needed. 

Boon, J.R and Duinker, J.C. (1985). Kinetics of polychlorinated biphenyl (PCB) components in juvenile sole Solea solea) in relation to concentrations in water and to hpid metabolism under conditions of starvation. Aquatic Toxicology, 7 119-134. 

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