Metabolism mechanisms excretion

The mechanisms of the metabolism and excretion of P-carotene are not clear, other than the identification of a number of partially oxidised intermediates found in plasma (Khachik et al., 1992). It is assumed that the carotenoids are metabolised in a manner analogous to the P-oxidation of fatty acids although there is no evidence for this. 

Repeat dose pharmacokinetic studies were undertaken in Sprague-Dawley rats and in monkeys. Biodistribution studies were carried out in both normal and knockout mice, with the majority of product distributed to the liver. No specific studies on product metabolism or excretion were undertaken, as the protein is almost certainly degraded via normal protein degradation mechanisms. 

Fish rapidly absorb, metabolize, and excrete chlorpyrifos from the diet (Barron etal. 1991). The mechanism of action of chlorpyrifos occurs via phosphorylation of the active site of acetylcholinesterase after initial formation of chlorpyrifos oxon by oxidative desulfuration. In studies with channel catfish (Ictalurus punctatus), the oral bioavailability of chlorpyrifos was 41%, substantially higher than in mammals. Catfish muscle contained less than 5% of the oral dose with an... 

Although there is no reason to suspect that the pharmacokinetics of 1,4-dichlorobenzene differs in children and adults, scant data are available to support or disprove this statement. Studies of absorption, distribution, metabolism, and excretion in children would aid in determining if children are at an increased risk, particularly if conducted in an area where a high-dose acute or low-dose chronic exposure to an environmental source were to occur. With regard to exposure during development, additional research on maternal and fetal/neonatal toxicokinetics, placental biotransformation, the mechanism of... 

The newer physiologically based pharmacokinetic (PBPK) models take nonlinearity of physiological processes such as chemical metabolism and excretion into consideration. At the high dose levels used in animal experiments, these mechanisms become saturated with the result that the tissues may be exposed to a different composition of pure compound and metabolites than at the low dose levels encountered in real-life human exposure. 

Mecfianism of Action A cyclic polypeptide antimicrobial but the mechanism of action is not well understood. Therapeutic Effect Suppresses mycobacterial multiplication. Pharmacokinetics Not well absorbed from the GI tract. Undergoes little metabolism. Primarily excreted unchanged in urine. Haif-iife 4-6 hr (half-life is increased with impaired renal function). 

Mechanism of Action A third-generation cephalosporin that binds to bacterial cell membranes and inhibits cell wall synthesis. Therapeutic Effect Bactericidal. Pharmacokinetics Moderately absorbed from the G1 tract. Protein binding 60%-70%. Widely distributed. Not appreciably metabolized. Primarily excreted unchanged in urine. Minimally removed by hemodialysis. Half-life 1 -2 hr (increased in impaired renal function). 

Mechanism of Action An antibacterial that prevents bacterial cell wall formation by inhibiting the synthesis of pepf idoglycan. Therapeutic Effect Bactericidal. Pharmacokinetics Rapidly absorbed following PO administration. Not bound to plasma proteins. Not metabolized. Partially excreted in urine minimal elimination in feces. Half-life 5.7 -i- 2.8 hr. 

Pharmacokinetic interactions occur when one drug interferes with the absorption, distribution, metabolism, or excretion of another drug so as to increase or decrease the concentration of free drug in the plasma (and at its site of action). Such interference may be two-way and may involve more than one mechanism. These may augment or counteract each other. 

Absorption of the quaternary carbamates from the conjunctiva, skin, and lungs is predictably poor, since their permanent charge renders them relatively insoluble in lipids. Thus, much larger doses are required for oral administration than for parenteral injection. Distribution into the central nervous system is negligible. Physostigmine, in contrast, is well absorbed from all sites and can be used topically in the eye (Table 7-4). It is distributed into the central nervous system and is more toxic than the more polar quaternary carbamates. The carbamates are relatively stable in aqueous solution but can be metabolized by nonspecific esterases in the body as well as by cholinesterase. However, the duration of their effect is determined chiefly by the stability of the inhibitor-enzyme complex (see Mechanism of Action, below), not by metabolism or excretion. 

Several models have been developed to simulate the absorption, distribution, metabolism and excretion of butadiene, some of its metabolites and its adducts to haemoglobin in mouse, rat and man. Critical aspects are discussed in Csanady et al. (1996) and in Himmelstein et al. (1997). Basically, the models consist of a number of compartments representing diverse tissues and organs, several of which are grouped together. These compartments are linked by blood flow. The main differences between models are the number of metabolizing and nonmetabolizing compartments, the mechanisms of metabolism, the metabolites taken into consideration, and the values of the biochemical. 

Deacetylation. Deacetylation occurs in a number of species, but there is a large difference between species, strains, and individuals in the extent to which the reaction occurs. Because acetylation and deacetylation are catalyzed by different enzymes, the levels of which vary independently in different species, the importance of deacetylation as a xenobiotic metabolizing mechanism also varies between species. This can be seen in a comparison of the rabbit and the dog. The rabbit, which has high acetyltransferase activity and low deacetylase, excretes significant amounts of acetylated amines. The dog, in which the opposite situation obtains, does not. 

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