Biotransformation and elimination

Olson LE, JL Allen, JW Hogan (1977) Biotransformation and elimination of the herbicide dinitramine in carp. J Agric Food Chem 25 554-556. 

Despite all the problems attendant on studies of aquatic animals, however, great strides have been made in the past 10 years in defining biochemical pathways used by fishes to biotransform and eliminate xenobiotics (2, 3, 4, 5). Many of the earlier studies, especially the extensive work of DeWaide (6), defined various biochemical transformations which xenobiotics may undergo in vitro. Only in the past 10 years have in vivo studies been undertaken to define the routes and rates of elimination of xenobiotics by fishes (7, 8, 9, 10, ll). 

When only a fixed amount of drug is eliminated in a given interval of time, because enzymes for biotransformation and elimination are saturated, the kinetics of drug elimination are zero order (16). Alcohol is the classic example, where blood levels rise exponentially with increased amounts ingested, because elimination mechanisms are saturated and only a certain fraction of the total dose taken can be eliminated before the next dose is ingested. 

First-order kinetics The amount of drug eliminated per unit of time is directly proportional to its concentration. In this state, the mechanisms for biotransformation and elimination are not saturated (e.g., benzodiazepines, tricyclic antidepressants, lithium carbonate). 

Pyrantel exliibits absorption, distribution, biotransformation, and elimination profiles similar to those of morantel. Pyrantel tartrate is well absorbed with peak plasma levels occurring 2-3 h after dosing. In ruminants, urinary excretion accounts for about 25% of the administered dose, while much of the remainder passes unchanged in feces. However, the pamoate salt is very poorly absorbed, most of the dose being excreted in feces. 

Renton KW. Alteration of drug biotransformation and elimination during infection and inflammation. Pharmacol Ther 2001 92 147-163. 

Primary objective To investigate the absorption, distribution, biotransformation and elimination of XYZ1234 in healthy men following oral administration of 14CXYZ1234. This includes (i) overall balance of excretion of the administered radioactivity... 

Absorption, distribution, biotransformation, and elimination are interrelated processes as illustrated in Figure 9.27. j.l Absorption... 

The two most important organs for biotransformation and elimination are the liver and the kidneys. 

Arsenic toxicity from drinking water is a major public health concern in many countries throughout the world. If exposure is to the inorganic form, the kidneys are the target organ due to its involvement in in vivo biotransformation and elimination. Very few clinical cases of toxicity are reported in humans. Most clinical cases of toxicosis are reported in animals, especially cattle and dogs, by... 

Drugs are transported in the aqueous phase of blood plasma. To have an effect, drugs must enter cells or reach cell membrane receptors. All aspects of the absorption, distribution, biotransformation and elimination of drugs involve transfer across cell membranes. Other barriers, including multiple layers of cells (e.g. the intestinal epithelium or epidermis), also exist. 

The glycoproteins (ricin) are poorly absorbed from the gastrointestinal tract however, once absorbed, they most likely follow a distribution pattern similar to that of albumin. Many cell surfaces contain receptors specific for the ricin molecules. This molecule consists of two subunits, A and B, bound by a disulfide link. When this link is broken, the B subunit binds to galactose-containing receptors in the cell wall and is transported intracellularly. The A subunit inhibits protein synthesis. The liver, spleen, adrenal cortex, and bone marrow are the primary sites of distribution. The biotransformation and elimination of toxalbumins are poorly understood. The elimination half-life in one patient was 2 days. The reported disappearance of ricin from the plasma is according to first-order kinetics when... 

The mature bean is innocuous if the hard outer coat is intact. Any interruption in the integrity of the seed coat (e.g., chewing) or ingestion of the soft-coated immature bean may cause toxicity. The inner core contains the amino acid n-methyltryptophan, abric acid, glycyrrhizin, and abrin. Abrin is stable in the gastrointestinal tract where it is slowly, but erratically absorbed. In rats, distribution sites occur primarily in the liver (12%) and spleen. Biotransformation and elimination of toxalbumins are poorly defined. 

Glutathione (GSH Fig. 4.2), is perhaps the most important of the Phase II enzymes in the biotransformation and elimination of xenobiotics. It also defends cells against oxidative stress (see later). 

Finally, species differences in the induction of individual or multiple biotransformation and elimination pathways can lead to the production of different metabolite profiles in humans compared to animal models. The FDA... 

Aquatic vascular plants and macroalgae can take up TNT dissolved in water very efficiently as indicated by removal rates determined for several species [11,12] some of which are promoted for use in phyto-treatment of explosives-contaminated water [11]. Less efficient removal of dissolved RDX was reported for wetland and aquatic plants [13,14], Efficient biotransformation and elimination mechanisms in aquatic vascular plants and macroalgae resulted in a lack of bioconcentration of TNT and its solvent-extractable transformation products [11,12], This chapter summarizes and discusses the bioconcentration, bioaccumulation, biotransformation, and toxicoki-netic processes of explosives in aquatic organisms. 

Most chemical toxicants are biotransformed and eliminated from the body in urine or bile however, some xenobiotics are not amenable to these transformations—that is, the body s enzyme systems are ineffective in transforming these compounds to more polar forms. Since these compounds are often very lipid soluble and cannot be quickly eliminated, the body stores them in our fat tissues throughout the body—a process known as bioaccumulation. In order for bioaccumulation to occur, a chemical toxicant must be absorbed faster than it is eliminated. These chemical toxicants are stored in the body s fat or lipids until a dynamic state is reached where the rates of absorption and elimination become about the same. The concentrations of these xenobiotics in fat tissues can be estimated from concentrations in blood that normally carries a small amount of circulating lipid, as reported in Incident 4.3.2.I. (See also in Section 4.2.1, Chemical Connection 4.2.1.1 Solubility, Storage, and Elimination.)... 

Biokinetic, or disposition, is the term for everything that happens to a chemical in the body. Thus, disposition of a chemical, or xenobiotic, is defined as the composite actions of its absorption, distribution, biotransformation, and elimination. 

The generic structures, technical names, physical and chemical properties, and tissue partition coefficients of the 15 pyrethroids and their metabolites are provided in Tables D1-D15 of Appendix D. Physical property values for modeling were obtained using a 2D model, ACD 12 (Advanced Chemistry Development, Inc., Toronto, Canada). A QSAR 3D model (i.e., QikProp 3.0 (Schrodinger, LL)), used in the development of (fraction unbound to plasma protein), indicated that the differences in physical binding properties between isomers were small. Differences, however, exist in chemical properties as noted in metabolism studies reviewed in Sect. 5. Biotransformation and elimination paths for the pyrethroids that are presented in Tables E1-E15 of Appendix E incorporate preliminary metabolic rate data for PBPK/PD model development. 

Table El Biotransformation and elimination paths of Allethrin and the resulting metabolites and preliminary liver Emax and values ...

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