Extent of Absorption

In this expression the only variable is N0 and it is this which governs the extent of absorption. Thus it follows that the integrated absorption coefficient is directly proportional to the concentration of the absorbing species. 

The data presented above suggest that methyl parathion would be absorbed by humans following ingestion of food and drinking water contaminated with methyl parathion. However, no data are available on the rate and extent of absorption in humans. 

Although the extent of absorption was not measured, the above evidence suggests that absorption in humans occurs rapidly following dermal exposure to commercial pesticide formulations of methyl parathion. 

Based on the rapid appearance of clinical signs and cholinesterase inhibition, methyl parathion appears to be readily absorbed by humans and animals following inhalation, oral, and dermal exposure. Following oral administration of methyl parathion to animals, the extent of absorption was at least 77-80% (Braeckman et al. 1983 Hollingworth et al. 1967). No studies were located regarding the extent of absorption following inhalation and dermal exposure, or the mechanism of absorption. 

Absorption, Distribution, Metabolism, and Excretion. Evidence of absorption comes from the occurrence of toxic effects following exposure to methyl parathion by all three routes (Fazekas 1971 Miyamoto et al. 1963b Nemec et al. 1968 Skiimer and Kilgore 1982b). These data indicate that the compound is absorbed by both humans and animals. No information is available to assess the relative rates and extent of absorption following inhalation and dermal exposure in humans or inhalation in animals. A dermal study in rats indicates that methyl parathion is rapidly absorbed through the skin (Abu-Qare et al. 2000). Additional data further indicate that methyl parathion is absorbed extensively and rapidly in humans and animals via oral and dermal routes of exposure (Braeckman et al. 1983 Flollingworth et al. 1967 Ware et al. 1973). However, additional toxicokinetic studies are needed to elucidate or further examine the efficiency and kinetics of absorption by all three exposure routes. 

Figure 24, The basic principle used in atomic absorption. The sample is sprayed into the flame, and the calcium and magnesium emission from the lamp is absorbed. The extent of absorption is measured on the detector arm translated in terms of concentration.

Rapid dermal absorption of trichloroethylene is evident from a study in which peak blood and exhaled air concentrations occurred within 5 minutes after a human subject immersed one hand in a solution of unspecified trichloroethylene concentration for 30 minutes (Sato and Nakajima 1978). Studies on dermal absorption of trichloroethylene in humans, as well as animals, are complicated by the fact that exposure in these studies is usually by direct contact of the skin with the undiluted chemical. Trichloroethylene is a lipophilic solvent that defats the skin and disrupts the stratum comeum, thereby enhancing its own absorption. Thus, the rate of absorption probably increases in a nonlinear fashion with greater epidermal disruption. Although the extent of absorption through the skin may be relatively modest with normal industrial use (Sato and Nakajima 1978 Stewart and Dodd 1964), there is insufficient information to evaluate the effects of chronic, low-level exposure in hiunans, especially when multiple routes may be involved. 

Thus, to explore the mechanisms of action of phytochemicals and their role in health promotion, an understanding of the factors that constrain their release from the foods in which they are contained, their extent of absorption and their fate in genetically diverse individuals is crucial. 

All the actual or putative functional benefits of carotenoids are dependent on their bioavailability amounts consumed, amounts released from the food structure during digestion and extent of absorption and tissue distribution. The following three sections deal with each of these issues in turn. 

The pigment identification is performed by the recognition of its characteristic absorption spectra. The pigment quantification is revealed by the extent of absorption (optical density). Each of these properties may be modulated by the direct environment into which the pigment molecule is incorporated. We look at this in some detail. 

In contrast to previous in vivo models, this in vitro model provides the possibility of dissociating experimentally two important processes of intestinal absorption cellular uptake and secretion. Under conditions mimicking the postprandial state (taurocholate/oleic acid supplementation), differentiated Caco-2 cells were able to (1) take up carotenoids at the apical sides and incorporate them into CMs and (2) secrete them at the basolateral sides associated with CM fractions. Using this approach, the extent of absorption of P-carotene through Caco-2 cell monolayers after 16 hr of incubation was 11.2%, a value falling within the in vivo range (9 to 22%). ° - Of the total amount of P-carotene secreted, 78% was associated with the two CM fractions and 10% with the VLDL fraction. ... 

The food matrix including its fiber and lipid content and concentrations of other carotenoids in the diet may influence the extent of absorption of carotenoid compounds. The relative absorption of lutein from a mixed vegetable diet was lower than from a diet containing pure lutein. A mixed preparation of lutein and zeaxanthin did not influence the absorption of P-carotene. 

Letrozole is another selective aromatase that inhibits the conversion of androgens to estrogen. Maximum plasma concentrations occur 1 hour after oral dosing concomitant food has not been shown to have an effect on the extent of absorption of letrazole. The terminal half-life is approximately 2 days. Letrozole is used in the treatment of postmenopausal women with hormone-receptor-positive or unknown advanced breast cancer. Side effects include bone pain, hot flushes, back pain, nausea, arthralgia, osteoporosis/bone fractures, and dyspnea. 

No data were located regarding absorption in animals after inhalation exposure to organophosphate ester hydraulic fluids or specific organophosphate esters, except for the observation that parent material was not detected by gas chromatography in the blood or urine of male rats exposed to 5,120 mg/m3 of an aerosol of a cyclotriphosphazene (99.9%) hydraulic fluid for 4 hours, thereby suggesting that the extent of absorption was limited (Kinkead and Bashe 1987). Blood samples were collected at 0, 24, and 48 hours after exposure was terminated. Urine was collected for 24 hours after exposure. 

Experiments with rats given oral doses of tritiated food-grade mineral oil provide supporting evidence that the absorption of hydrocarbons in mineral oils is limited. Five hours after dosing with 0.66 mL/kg of tritiated mineral oil ("liquid petrolatum U.S.P."), -75% of the administered radioactivity remained in the alimentary tract, and only 3% of the administered radioactivity was accounted for by radioactivity in other parts of the rat carcass (Ebert et al. 1966). About 80% of the administered radioactivity was recovered in feces during the first 2 days after treatment, and over 90% of the radioactivity in the feces was in the form of mineral oil. These data are consistent with the hypothesis that ingested mineral oil was poorly absorbed. Neither biliary excretion nor enterohepatic circulation of mineral oils was measured in this study, and thus, any quantitative estimates of the extent of absorption based on these data should be viewed as tentative. 

Organophosphate Ester Hydraulic Fluids. Information regarding the extent of absorption of organophosphate ester hydraulic fluids by the skin, lungs and gastrointestinal tract is very limited and the mechanism by which the organophosphate components of the fluids may enter the blood is unknown. 

These mixing motions will tend to improve drug absorption for two reasons. Any factor that increases rate of dissolution will increase the rate (and possibly the extent) of absorption, especially for poorly water-soluble drugs (BCS Classes II and IV). Since rate of dissolution depends on agitation intensity, mixing movements will tend to increase dissolution rate and thereby influence absorption. As rate of absorption depends directly on membrane surface area, and since mixing increases the contact area between drug and... 

As discussed previously, drug absorption may be impaired or improved when food is present in the GIT. Food may reduce the rate or extent of absorption by virtue of reduced gastric-emptying rate, which is particularly important for compounds unstable in gastric fluids and for dosage forms designed to release drug... 

Another important type of physical chemical interaction that may alter absorption is that of drug binding or adsorption onto the surface of another material. As with complexation and micellarization, adsorption will reduce the effective concentration gradient between gut fluids and the bloodstream, which is the driving force for passive absorption. While adsorption frequently reduces the rate of absorption, the interaction is often readily reversible and will not affect the extent of absorption. A major exception is adsorption onto charcoal, which in many cases appears to be irreversible, at least during the time of residence within the GIT. As a result, charcoal often reduces the extent of drug absorption. Indeed, this fact... 

In Sec. VII we dealt with methods of determining the rate (and mechanism) of absorption. In this section we will deal with methods of determining the extent of absorption. In every example, the calculation will involve a comparison between two studies carried out in the same group of volunteers on different occasions. Usually it will be necessary to assume that the volunteers behaved identically on both occasions, especially with regard to their pharmacokinetic parameters. 

Figure 3 illustrates a situation in which this may not be true. When 250 mL of water was taken with erythromycin tablets, the extent of absorption was much greater than when the tablets were taken with only 20 mL of water. In the latter case, dissolution probably did not occur under sink conditions. Hence, the dissolution rate decreased, and it appears that not all of the erythromycin had a chance to dissolve in the GIT. Note than the dissolution was not, however, the ratedetermining step in absorption, since the time to reach the peak concentration was the same in all situations. 

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