Absorption, Distribution and Excretion

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. 

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

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. 

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. 

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. 

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. 

G18. Grasbeck, R., Physiology and pathology of vitamin B12 absorption, distribution and excretion. Advances in Clin. Chem. 3, 299-366 (1960). 

Vitamin Br, Absorption, Distribution, and Excretion, Physiology and Pathology of (Grasbeck), 3, 299 Vitamins, Microbiological Assay Methods for (Baker and Sobotka), 5, 173... 

FACTORS SUCH AS CHARGE THAT AFFECT DRUG ABSORPTION, DISTRIBUTION, AND EXCRETION... 

Kerberle, H. (1971). Physicochemical factors of drugs affecting absorption, distribution and excretion. Acta Pharmacol. Toxicol. 29 (Suppl 3) 30-47. 

Drug metabolism has been recognized as one of the key factors in the discovery of new chemical entities. A lead compound needs to not only interact with the target enzyme/receptor but also remain over a certain threshold concentration at the site of action for a defined period to produce the desired therapeutic effect. Drug metabolism together with absorption, distribution and excretion are among the factors that influence the final time-concentration relationship of drugs and therefore the potential efficacy of the compound [1],... 

In addition to phase I and phase II enzymes, equally important is a group of transporter proteins expressed in various tissues, such as the liver, intestine, brain and kidney, which modulate the absorption, distribution and excretion of many drugs. 

This section presents a brief overview of any known mechanisms of metabolism, absorption, distribution, and excretion including substance reactions or physiological processes that lead to or comprise the mechanism(s) of toxic effect. 

Chu I, Villeneuve DC, Secours V, et al. 1979b. The absorption, distribution and excretion of photomirex in the rat. Drug Metab Dispos 7 24-27. 

Absorption, Distribution, Metabolism, and Excretion. No studies were located regarding the absorption, distribution, metabolism, and excretion of disulfoton by humans or animals after inhalation or dermal exposure. Limited data exist regarding the absorption, distribution, and excretion after oral exposure to disulfoton. Data on levels of disulfoton and metabolites excreted in urine and expired air suggest that some almost complete absorption of an administered dose of disulfoton over 3-10 days (Lee et al. 1985 Puhl and Fredrickson 1975). The data are limited regarding the relative rate and extent of absorption. Animal data suggest that disulfoton and/or its metabolites are rapidly distributed to the liver, kidney, fat, skin, muscle, and brain, with peak levels occurring within 6 hours (Puhl and Fredrickson 1975). Elimination of disulfoton and metabolites occurs primarily in the urine, with >90% excreted in the urine in 3-10 days (Lee et al. 1985 Puhl and Fredrickson 1975). 

Evidence further suggests that male rats eliminate disulfoton at a faster rate than females. This difference may be due to differences in absorption, metabolism, retention, excretion, or a combination of factors. The metabolic pathways of disulfoton are relatively well understood based on data from animal studies (Bull 1965 Lee et al. 1985 March et al. 1957 Puhl and Fredrickson 1975). Similar metabolites have been detected in the urine and tissues from humans exposed to disulfoton (Brokopp et al. 1981 Yashiki et al. 1990). One study suggests that a greater percentage of disulfoton sulfoxide is oxidized to demeton S-sulfoxide, rather than disulfoton sulfone to form demeton S-sulfone (Bull 1965). Additional studies in animals, designed to measure the rate and extent of absorption, distribution, and excretion of disulfoton after inhalation or dermal exposure would be useful for predicting the toxicokinetics of disulfoton in humans at an occupational or hazardous waste site. 

Odani, T., Tanizawa, H., and Takino, Y. (1983a). Studies on the absorption, distribution, excretion and metabolism of ginseng saponins. 11. The absorption, distribution and excretion of ginsenoside Rgi in the rat. Chem. Pharm. Bull. 31, 292-298. 

Comparative Toxicokinetics. Available studies indicate that bromomethane affects the same target tissues in humans and animals, although there are apparent differences in sensitivity between species, with rabbits being more sensitive than rats or mice (Irish et al. 1940). However, quantitative toxicokinetic data on absorption, distribution, and excretion are available only for rats (Bond et al. 1985 Gargas and Andersen 1982 Honma et al. 1985 Jaskot et al. 1988 Medinsky et al. 1984, 1985). Additional toxicokinetic studies would be helpful in understanding the basis of the... 

Mink FL, Brown TJ, Rickabaugh J. 1986. Absorption, distribution and excretion of C-trihalomethanes in mice and rats. Bull Environ Contam Toxicol 37 752-758. 

Ono C, Takao A, Atsumi R. (2004) Absorption, distribution, and excretion of DJ-927, a novel orally effective taxane, in mice, dogs, and monkeys. Biol Pharm Bull 27 345-351. 

Physiology and Pathology of Vitamin Bj, Absorption, Distribution, and Excretion Ralph Grdsbeck... 

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