Intestinal absorption mechanisms

In foods vitamin B2 occurs free or combined both as FAD and FMN and complexed with proteins. Riboflavin is widely distributed in foodstnffs, but there are very few rich sources. Only yeast and liver contain more than 2mg/100g. Other good sources are milk, the white of eggs, fish roe, kidney, and leafy vegetables. Since riboflavin is continuously excreted in the urine, deficiency is qnite common when dietary intake is insufficient. The symptoms of deficiency are cracked and red lips, inflammation of the lining of the month and tongue, mouth ulcers, cracks at the comer of the mouth, and sore throat. Overdose of oral intake present low toxicity, probably explained by the limited capacity of the intestinal absorption mechanism [417]. 

Chow, S.L., and D. Hollander. 1978. Arachidonic acid intestinal absorption Mechanism of transport and influence of luminal factors of absorption in vitro. Lipids 13 768. 

The intestinal absorption mechanisms of amino acids and di- and tripeptides are characterized relatively well, as described above. However, only a limited amount of work has been published for the absorption of tetra- and higher peptides, and the results are somewhat mixed. In general, it appears that tetra- or higher peptides are not well absorbed from the GI tract. Table 2 shows the oral bioavaiability of peptides and peptide-like drugs (molecular weight <1500). 

Friedman DI, Amidon GL. Intestinal absorption mechanism of dipeptide angiotensin converting enzyme inhibitors of the lysyl-proline type hsinopril and SQ 29,852. J Pharm Sci 1989 78(12) 995-8. 

A study in 7 subjects found that 20 mg of intravenous metoclopramide increased the rate of alcohol absorption, and the peak blood levels were raised from 55 to 86 mg%. Similar results were seen in 2 healthy subjects given metoclopramide orally. Another study in 7 healthy subjects found that 10 mg of intravenous metoclopramide accelerated the rate of absorption of alcohol 70 mg/kg given orally, and increased its peak levels, but not to a statistically significant extent. Blood alcohol levels remained below 12 mg%. More importantly the sedative effects of the alcohol were increased. The reasons for this effect are not fully understood, but it appears to be related to an increase in gastric emptying. These two studies were done to find out more about intestinal absorption mechanisms rather than to identify daily practicalities, so the importance of the findings is uncertain. However, it seems possible that the effects of alcohol will be increased. Metoclopramide alone can sometimes cause drowsiness, and if affected, patients should not drive or operate machinery. 

Friedman, D. I., and Amidon, G. L., 1989a, Intestinal absorption mechanism of two prodmg ACE inhibitors in rats Enalapril maleate and fosinopril sodium, Pliorw. Res. 6 1043-1047. Friedman, D. I., and Amidon, G. L., 1989b, The intestinal absorption mechanism of dipeptide ACE inhibitors of the lysyl-proline type Lisonopril and SQ 29,852, Pharm. Sci. 78 995-998. 

NaMshima, E., Tsuji, A., Kagatani, S., and Yamana, T., 1984, Intestinal absorption mechanism of amino-(3-lactam antibiotics. III. Kinetics of carrier-mediated transport across the rat small intestine in situ, J. Pharmacobio-Dyn. 7 452-464. 

Yee, A., and Amidon, G. L., 1990, Intestinal absorption mechanism of three angiotensin-converting enz5Tne inhibitors Quinapril, benazepril and CGS16617, Pharm. Sci 7 S-155. 

Yokohama, S., Yoshioka, T., Yamashita, K., and Kitamori, N., 1984b, Intestinal absorption mechanisms of thyrotropin releasing hormone, J. Pharmacobio-Dyn. 7 44 51. 

Contraction of muscle follows an increase of Ca " in the muscle cell as a result of nerve stimulation. This initiates processes which cause the proteins myosin and actin to be drawn together making the cell shorter and thicker. The return of the Ca " to its storage site, the sarcoplasmic reticulum, by an active pump mechanism allows the contracted muscle to relax (27). Calcium ion, also a factor in the release of acetylcholine on stimulation of nerve cells, influences the permeabiUty of cell membranes activates enzymes, such as adenosine triphosphatase (ATPase), Hpase, and some proteolytic enzymes and facihtates intestinal absorption of vitamin B 2 [68-19-9] (28). 

Absorption. An absorption mechanism capable of handling between 1.5 to 3.0 pg of vitamin responsible for most of the intestinal... 

Although it is being found that vitamin D metaboUtes play a role ia many different biological functions, metaboHsm primarily occurs to maintain the calcium homeostasis of the body. When calcium semm levels fall below the normal range, 1 a,25-dihydroxy-vitainin is made when calcium levels are at or above this level, 24,25-dihydroxycholecalciferol is made, and 1 a-hydroxylase activity is discontiaued. The calcium homeostasis mechanism iavolves a hypocalcemic stimulus, which iaduces the secretion of parathyroid hormone. This causes phosphate diuresis ia the kidney, which stimulates the 1 a-hydroxylase activity and causes the hydroxylation of 25-hydroxy-vitamin D to 1 a,25-dihydroxycholecalciferol. Parathyroid hormone and 1,25-dihydroxycholecalciferol act at the bone site cooperatively to stimulate calcium mobilization from the bone (see Hormones). Calcium blood levels are also iafluenced by the effects of the metaboUte on intestinal absorption and renal resorption. 

Diabetic patients have reduced antioxidant defences and suffer from an increased risk of free radical-mediated diseases such as coronary heart disease. EC has a pronounced insulin-like effect on erythrocyte membrane-bound acetylcholinesterase in type II diabetic patients (Rizvi and Zaid, 2001). Tea polyphenols were shown to possess anti-diabetic activity and to be effective both in the prevention and treatment of diabetes (Choi et al, 1998 Yang et al, 1999). The main mechanism by which tea polyphenols appear to lower serum glucose levels is via the inhibition of the activity of the starch digesting enzyme, amylase. Tea inhibits both salivary and intestinal amylase, so that starch is broken down more slowly and the rise in serum glucose is thus reduced. In addition, tea may affect the intestinal absorption of glucose. 

Based on the limitations of using human subjects, simple alternative in vitro models were developed to investigate mechanisms involved in the intestinal absorption process of a compound of interest and to screen the relative bioavailability of a compound from various food matrices. However, the data generated from in vitro approaches must be taken with caution because they are obtained under relatively simplified and static conditions compared to dynamic physiological in vivo conditions. Indeed, the overall bioavailability of a compound is the result of several complex steps that are influenced by many factors including factors present in the gastrointestinal lumen and intestinal cells as described later. Nevertheless, these in vitro approaches are useful tools for guiding further smdies in humans. 

FIGURE 29-2. Levodopa absorption and metabolism. Levodopa is absorbed in the small intestine and is distributed into the plasma and brain compartments by an active transport mechanism. Levodopa is metabolized by dopa decarboxylase, monoamine oxidase, and catechol-O-methyltransferase. Carbidopa does not cross the blood-brain barrier. Large, neutral amino acids in food compete with levodopa for intestinal absorption (transport across gut endothelium to plasma). They also compete for transport across the brain (plasma compartment to brain compartment). Food and anticholinergics delay gastric emptying resulting in levodopa degradation in the stomach and a decreased amount of levodopa absorbed. If the interaction becomes a problem, administer levodopa 30 minutes before or 60 minutes after meals. 

Since many essential nutrients (e.g., monosaccharides, amino acids, and vitamins) are water-soluble, they have low oil/water partition coefficients, which would suggest poor absorption from the GIT. However, to ensure adequate uptake of these materials from food, the intestine has developed specialized absorption mechanisms that depend on membrane participation and require the compound to have a specific chemical structure. Since these processes are discussed in Chapter 4, we will not dwell on them here. This carrier transport mechanism is illustrated in Fig. 9C. Absorption by a specialized carrier mechanism (from the rat intestine) has been shown to exist for several agents used in cancer chemotherapy (5-fluorouracil and 5-bromouracil) [37,38], which may be considered false nutrients in that their chemical structures are very similar to essential nutrients for which the intestine has a specialized transport mechanism. It would be instructive to examine some studies concerned with riboflavin and ascorbic acid absorption in humans, as these illustrate how one may treat urine data to explore the mechanism of absorption. If a compound is... 

CAM Hogben, DJ Tocco, BB Brodie, LS Schanker. On the mechanism of intestinal absorption of drugs. J Pharmacol Exp Ther 125 275-282, 1959. 

BH Stewart, AR Kugler, PR Thompson, NN Bock-brader. A saturable transport mechanism in the intestinal absorption of gabapentin is the underlying cause of the lack of proportionality between increasing dose and drug levels in plasma. Pharmaceut Res 10 276-281, 1993. 

Numerous observations of non-linear relationships between PbB concentration and lead intake in humans provide further support for the existence of a saturable absorption mechanism or some other capacity limited process in the distribution of lead in humans (Pocock et al. 1983 Sherlock et al. 1984, 1986). However, in immature swine that received oral doses of lead in soil, lead dose-blood lead relationships were non-linear whereas, dose-tissue lead relationships for bone, kidney and liver were linear. The same pattern (nonlinearity for PbB and linearity for tissues) was observed in swine administered lead acetate intravenously (Casteel et al. 1997). These results suggest that the non-linearity in the lead dose-PbB relationship may derive from an effect of lead dose on some aspect of the biokinetics of lead other than absorption. Evidence from mechanistic studies for capacity-limited processes at the level of the intestinal epithelium is compelling, which would suggest that the intake-uptake relationship for lead is likely to be non-linear these studies are discussed in greater detail in Section 2.4.1. 

Mechanisms of Intestinal Absorption of Carotenoids Insights from In Vitro Systems... 

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