Distribution and excretion

Pharmacodynamics is the study of dmg action primarily in terms of dmg stmcture, site of action, and the biochemical and physiological consequences of the dmg action. The availabiUty of a dmg at its site of action is deterrnined by several processes (Fig. 1), including absorption, metaboHsm, distribution, and excretion. These processes constitute the pharmacokinetic aspects of dmg action. The onset, intensity, and duration of dmg action are deterrnined by these factors as well as by the avadabihty of the dmg at its receptor site(s) and the events initiated by receptor activation (see Drug delivery). 

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. 

In general, the higher the foaming power, the lower the toxicity (39). Sulfonates that are absorbed into a living system are readily distributed and excreted. 

Although the antibacterial spectmm is similar for many of the sulfas, chemical modifications of the parent molecule have produced compounds with a variety of absorption, metaboHsm, tissue distribution, and excretion characteristics. Administration is typically oral or by injection. When absorbed, they tend to distribute widely in the body, be metabolized by the Hver, and excreted in the urine. Toxic reactions or untoward side effects have been characterized as blood dyscrasias crystal deposition in the kidneys, especially with insufficient urinary output and allergic sensitization. Selection of organisms resistant to the sulfonamides has been observed, but has not been correlated with cross-resistance to other antibiotic families (see Antibacterial AGENTS, synthetic-sulfonamides). 

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

The behavior of calcium in the cells can be considered as a metabolic process. There is uptake, distribution, and excretion of calcium in the cells. The uptake of calcium occurs via activation of calcium channels. The end result is elevation of intracellular calcium levels and subsequent activation. Be-... 

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. 

Penninks AH, Hilgers L, Seinen W (1987) The absorption, tissue distribution and excretion of di-n-octyltin dichloride in rats. Toxicology, 44 107-120. 

In this study the tissue distribution and excretion of activity has been evaluated in rats following a single oral dose of TCDD- C. Almost 30% of the dose administered was eliminated via the feces during the first 48 hours following treatment. The excretion of activity via the... 

Durbin and Schmidt (1985) Model of Distribution and Excretion of Absorbed Americium in the Human... 

Durbin and Schmidt (1985) proposed a model for tissue distribution and excretion of absorbed americium in humans. A unique feature of this model is that transfers from plasma to tissues are assumed to be instantaneous therefore, a central plasma (and blood) compartment is not included in the model (see Figure 3-10). Tissue compartments included in the model are slow and fast turnover bone compartments, representing cortical and trabecular bone, respectively liver and slow and fast turnover for other soft tissue compartments. Excretion pathways include urine and feces. Urinary excretion is represented as a sum of the contributions from bone, liver, and other soft tissues. Fecal americium is assumed to be excreted from the liver. 

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. 

Hammond PB. 1971. The effects of chelating agents on the tissue distribution and excretion of lead. Toxicol Appl Pharmacol 18 296-310. 

Hayashi M, Yamamoto K, Yoshimura M, et al. 1993. Effects of fasting on distribution and excretion of lead following long-term lead exposure in rats. Arch Environ Contain Toxicol 24 201-205. 

Keller CA, Doherty RA. 1980b. Distribution and excretion of lead in young and adult female mice. Environ Res 21 217-228. 

Morgan A, Holmes A, Evans JC. 1977. Retention, distribution, and excretion of lead by the rat after intravenous injection. Br J Ind Med 34 37-42. 

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. 

Palmer, H. E., Crook, G. H. and Nelson, I. C. (1968). Uptake, Distribution, and Excretion of Promethium in Humans and the Effect of DTPA on these Parameters, Report No. BNWL-SA-1915, also Report No. CONF-680607 (Battelle-Northwest, Pacific Northwest Laboratories, Richland, Washington). 

Pinkerton, M.K., E.A.Hagan, and K.C.Back. 1967. Distribution and excretion of 14C-monomethylhydrazine. AMRL-TR-67-175. Aerospace Medical Research Laboratory, Wright-Patterson AFB, OH. 

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. 

Daabees, A.Y., N.A. El Domiaty, A.M. Hilmy, A.M. Awadallah, and E.M.A. Taleb. 1991. Mortality, distribution and excretion of cobalt and nickel administered subcutaneously to toads. Jour. Medical Res. Inst. (Egypt) 12 185-201. 

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

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