Absorption and distribution

Additional discussions are available in the General References concerning the properties of several nitrofiirans. This includes further coverage of the chemotherapeutic and physical properties antimicrobial activity bacterial resistance absorption, distribution, and excretion clinical use and safety studies, of this interesting class of antiinfective compounds. 

The absorption, distribution, and accumulation of lead in the human body may be represented by a three-part model (6). The first part consists of red blood cells, which move the lead to the other two parts, soft tissue and bone. The blood cells and soft tissue, represented by the liver and kidney, constitute the mobile part of the lead body burden, which can fluctuate depending on the length of exposure to the pollutant. Lead accumulation over a long period of time occurs in the bones, which store up to 95% of the total body burden. However, the lead in soft tissue represents a potentially greater toxicological hazard and is the more important component of the lead body burden. Lead measured in the urine has been found to be a good index of the amount of mobile lead in the body. The majority of lead is eliminated from the body in the urine and feces, with smaller amounts removed by sweat, hair, and nails. 

FIGURE 5.36 Schematic representation of absorption, distribution, and excretion of xenoblotics. ... 

Kinetic studies Rats/rniee One day to weeks Absorption, distribution, and elimination... 

Much work has also 4)een done bearing directly or indirectly on the mode of action of quinine and other anti-malarial drugs. The absorption, distribution and metabolism of quinine has been investigated by various workers of whom Kelsey, Ceiling, Oldham and Dearborn (1944)... 

It was apparent that the FDA recognized the ability of the pharmaceutical industry to develop chiral assays. With the advent of chiral stationary phases (CSPs) in the early 1980s [8, 9], the tools required to resolve enantiomers were entrenched, thus enabling the researcher the ability to quantify, characterize, and identify stereoisomers. Given these tools, the researcher can assess the pharmacology or toxicology and pharmacokinetic properties of enantiopure drugs for potential interconversion, absorption, distribution, and excretion of the individual enantiomers. 

Toxicokinetic—The study of the absorption, distribution and elimination of toxic compounds in the living organism. 

Austel V, Kutter E. Absorption, distribution, and metabolism of drugs. In Topliss, EJ, editor. Quantitative structure-activity relationships of drugs. New York Academic Press, 1983. p. 437-96. 

This is generally accepted as the term to describe the absorption distribution and metabolism of a drug in vivo and it is these factors which determine how quickly and how much of the administered drug can actually reach its site of action (in the CNS) and be maintained there for the required time (see Fig. 5.4). Experimentally drugs are... 

Figure 5,4 Pharmacokinetics. The absorption distribution and fate of drugs in the body. Routes of administration are shown on the left, excretion in the urine and faeces on the right. Drugs taken orally are absorbed from the stomach and intestine and must first pass through the portal circulation and liver where they may be metabolised. In the plasma much drug is bound to protein and only that which is free can pass through the capillaries and into tissue and organs. To cross the blood brain barrier, however, drugs have to be in an unionised lipid-soluble (lipophilic) form. This is also essential for the absorption of drugs from the intestine and their reabsorption in the kidney tubule. See text for further details...

FIG. 2 Mechanisms of drug transfer in the cellular layers that line different compartments in the body. These mechanisms regulate drug absorption, distribution, and elimination. The figure illustrates these mechanisms in the intestinal wall. (1) Passive transcellular diffusion across the lipid bilayers, (2) paracellular passive diffusion, (3) efflux by P-glycoprotein, (4) metabolism during drug absorption, (5) active transport, and (6) transcytosis [251]. 

One approach to formulating potential differences in ethnic response is to examine the metabolic pathways of the common antipsychotics and determine whether the known ethnic variations in metabolizing enzymes or other effects on absorption, distribution, and excretion can be applied a priori to predict potential clinical effects. In this section we will consider some of the commonly prescribed SGAs, and only briefly touch on the FGAs. 

The pharmacology and toxicology of certain economic poisons have been developed to a degree which surpasses investigations of any other class of nonmedicinal compounds. In certain instances more is known concerning the site and mechanism of action, the absorption, distribution, and excretion of these substances than is known concerning some of the more commonly used pharmaceutical compounds. This has come about as a result of the conscientious recognition of the public health hazards which are inherent in the economic poisons. 

Abou-Donia MB, Suwita E, Nomeir AA. 1990a. Absorption, distribution, and elimination of a single oral dose of [14C]tri-orf/ o-cresyl phosphate in hens. Toxicology 61 13-25. 

V Austel, E Kutter. Absorption, distribution and metabolism of drugs. In IG Topless, ed. Quantitative Structure-Activity Relationships of Drugs. New York Academic Press, 1980, pp 437-496. 

Ayrton, A., Morgan, P., Role of transport proteins in drug absorption, distribution and excretion, Xenobiotica 2001, 31, 469-497. 

Ohzawa et al [112] studied the absorption, distribution, and excretion of 14C miconazole in rats after a single administration. After the intravenous administration of 14C miconazole at a dose of 10 mg/kg to the male rats, the plasma concentration of radioactivity declined biophysically with half-lives of 0.76 h (a phase) and 10.32 h (/ phase). After oral administration of 14C miconazole at a dose of 1, 3, or 10 mg/kg to male rats, the plasma concentration of radioactivity reached the maximum level within 1.25 h, after dosing and the decline of radioactivity after the maximum level was similar to that after intravenous administration. At a dose of 30 mg/kg, the pharmacokinetic profile of radioactivity in the plasma was different from that at the lower doses. In the female rats, the plasma concentration of radioactivity declined more slowly than that in male rats. The tests were conducted on pregnant rats, lactating rats, bile-duct cumulated male rats. Enterohepatic circulation was observed. In the in situ experiment, 14C miconazole injected was observed from the duodenum, jejunum, and/or ileum, but not from the stomach. 

Ohzawa et al [114] studied the absorption, distribution, and excretion of 14C miconazole in male rats during and after consecutive oral administration at a dose of 10 mg/kg once a day for 15 days. During consecutive administration, the plasma concentration of radioactivity reached the steady state on day 4 and was 0.48 approximately 0.52 pg eq./mL at 24 h after each dose. After the final dose, the plasma concentration of radioactivity reached the maximum level of 1.67 pg eq./ mL at 7.5 h and declined with a half-life of about 18.68 h. The area under the curve 24 h was 28.3 pg h/mL, which is close to the area under the curve O-oo of a single oral dose. 

The answers are 31-b, 32-a, 33-d (Katzung, pp 4—7.) The absorption, distribution, and elimination of drugs require that they cross various cellular membranes The descriptions that are given in the question define the various transport mechanisms. The most common method by which ionic compounds of low molecular weight (100 to 200) enter cells is via membrane channels. The degree to which such filtration occurs varies from cell type to cell type because their pore sizes differ. 

Simple diffusion is another mechanism by which substances cross membranes without the active participation of components in the membranes. Generally, lipid-soluble substances employ this method to enter cells. Both simple diffusion and filtration are dominant factors in most drug absorption, distribution, and elimination. 

ATSDR (Agency for Toxic Substances and Disease Registry). 1994. Toxicological Profile for Hydrazine. Draft. U.S. Department of Health and Human Services, ATSDR, Atlanta, Ga. Back, K.C., M.K.Pinkerton, A.B.Cooper, and others. 1963. Absorption, distribution, and excretion of 1,1-dimethylhydrazine (UDMH). Toxicol. Appl. Pharmacol. 5 401—413. 

Hiles, R.A. 1974. Absorption, distribution, and excretion of inorganic tin in rats. Toxicol. Appl. Pharmacol. 27 366-379. 

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