Absorption intestinal

For the majority of drugs, the preferred administration route is by oral ingestion which requires good intestinal absorption of drug molecules. Intestinal absorption is usually expressed as fraction absorbed (FA), expressing the percentage of initial dose appearing in a portal vein [15]. 

PSA was also shown to play an important role in explaining human in vivo jejunum permeability [18]. A model based on PSA and calculated log P for the prediction of drug absorption [19] was developed for 199 well-absorbed and 35 

Since experimental determination of intestinal absorption is quite demanding, Caco-2 cell monolayers have been successfully used to model passive drug absorption. Several models for the prediction of Caco-2 permeability using PSA were developed, including those of van de Waterbeemd et al. [5] and Palm et al. [22] who found that relationships between Caco-2 permeability and PSA is stronger than with Clog D, Krarup et al. [23] who used dynamic PSA calculated for water accessible molecular surface and Bergstrom et al. [24]. 

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Diarrhea is a common problem that is usually self-limiting and of short duration. Increased accumulations of small intestinal and colonic contents are known to be responsible for producing diarrhea. The former may be caused by increased intestinal secretion which may be enterotoxin-induced, eg, cholera and E. col] or hormone and dmg-induced, eg, caffeine, prostaglandins, and laxatives decreased intestinal absorption because of decreased mucosal surface area, mucosal disease, eg, tropical spme, or osmotic deficiency, eg, disaccharidase or lactase deficiency and rapid transit of contents. An increased accumulation of colonic content may be linked to increased colonic secretion owing to hydroxy fatty acid or bile acids, and exudation, eg, inflammatory bowel disease or amebiasis decreased colonic absorption caused by decreased surface area, mucosal disease, and osmotic factors and rapid transit, eg, irritable bowel syndrome. 

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). 

Regulation of Serum Concentration. Regulation of semm Mg " appears to result from a balance among intestinal absorption, renal... 

Bde salts, cholesterol, phosphoHpids, and other minor components are secreted by the Hver. Bile salts serve three significant physiological functions. The hydrophilic carboxylate group, which is attached via an alkyl chain to the hydrophobic steroid skeleton, allows the bile salts to form water-soluble micelles with cholesterol and phosphoHpids in the bile. These micelles assist in the solvation of cholesterol. By solvating cholesterol, bile salts contribute to the homeostatic regulation of the amount of cholesterol in the whole body. Bile salts are also necessary for the intestinal absorption of dietary fats and fat-soluble vitamins (24—26). 

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. 

The overall effect in most animals is to stimulate intestinal absorption of calcium with a concomitant increase in semm calcium and a reduction in parathyroid hormone (PTH). Modest hypercalcemia allows the glomerular filtration rate to remain stable and hypercalciuria to occur because of increased filtered load of calcium and reduction of tubular resorption of calcium with reduced PTH. However, with further increases in semm calcium, the glomerular filtration rate decreases, resulting in an even more rapid increase in semm calcium and the subsequent fall in urinary calcium. 

Treatment. Treatment of poisoning from soluble barium salts may be preventive or curative (47,51). Preventive treatment involves inhibition of intestinal absorption by administering such soluble sulfates as magnesium or sodium, causing precipitation of barium sulfate in the alimentary tract. 

Vitamin D is a family of closely related molecules that prevent rickets, a childhood disease characterized by inadequate intestinal absorption and kidney reabsorption of calcium and phosphate. These inadequacies eventually lead to the demineralization of bones. The symptoms of rickets include bowlegs,... 

Human intestinal absorption of 5 (01JPS749) and 6 (01MI30) was predicted by using five Abraham descriptors and CaCo-2 monolayer, respectively. The effect of hydrophobicity and molecular mass on the accumulation of 10 fluoroquinolones, including 5, by Staphylococcus aureus were evaluated (01MI14). 

Intestinal absorption of digoxin is less complete compared to digitoxin. In order to improve absorption, acetylated- and methylated-digoxin derivates were developed. Digitoxin is metabolised in hepatic microsomal enzymes and can be cleared independently from renal function. The therapeutical serum level of digoxin is 0.5-2.0 ng/ml and 10-35 ng/ml of digitoxin. Steady state plateau of therapeutic plasma concentrations is reached after 4-5 half-life-times using standard daily doses [5]. 

In-vitro models can provide preliminary insights into some pharmacodynamic aspects. For example, cultured Caco 2 cell lines (derived from a human colorectal carcinoma) may be used to simulate intestinal absorption behaviour, while cultured hepatic cell lines are available for metabolic studies. However, a comprehensive understanding of the pharmacokinetic effects vfill require the use of in-vivo animal studies, where the drug levels in various tissues can be measured after different dosages and time intervals. Radioactively labelled drugs (carbon-14) may be used to facilitate detection. Animal model studies of human biopharmaceutical products may be compromised by immune responses that would not be expected when actually treating human subjects. 

PatU SD, Ngo LY, Glue P, Unadkat JD (1998) Intestinal absorption of ribavirin is preferentially mediated by the Na-l—nucleoside purine (Nl) transporter. Pharm Res 15 950-952... 

Taylor, E.W., Giboons, J.A., and Baeck-man, R.A. Intestinal absorption screening of mixtures from combinatorial libraries in the Caco-2 model. Pharm. Res. 1997, 14, 572-577. 

Yu LX, Lipka E, Crison JR and Amidon GL. Transport approaches to the bio-pharmaceutical design of oral drug delivery systems prediction of intestinal absorption. Adv Drug Deliv Rev 1996 19 359-76. 

Zmuidinavicius D, Didziapetris R, Japertas P, Avdeef A and Petrauskas A. Classification structure-activity relations (C-SAR) in prediction of human intestinal absorption. J Pharm Sci 2003 92 621-33. 

Parrott N, Lave T. Prediction of intestinal absorption comparative assessment of GASTROPLUS and IDEA . Eur J Pharm Sci 2002 17 51-61... 

In addition to its role in regulating calcium homeostasis, vitamin D is required for the intestinal absorption of calcium. Synthesis of the intracellular calciumbinding protein, calbindin, required for calcium absorption, is induced by vitamin D, which also affects the permeability of the mucosal cells to calcium, an effect that is rapid and independent of protein synthesis. 

D Calciferol Maintenance of calcium balance enhances intestinal absorption of Ca and mobilizes bone mineral Rickets = poor mineralization of bone osteomalacia = bone demineralization... 

FURR H c and clark r m (1997) Intestinal absorption and tissue distribution of carotenoids. J Nutr Biochem. 8(7) 364-77. 

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. 

IKEDA I, IMASATO Y, SASAKI E, NAKAYAMA M, NAGAO H, TAKEO T, YAYABE F, SUGANO M (1992) Tea catechins decrease micellar solubility and intestinal absorption of cholesterol in rats. Biochim Biophys Acta. 1127 141-6. 

KREYDIYYEH s I (1996) Inhibitors in tea of intestinal absorption of phenylalanine in rats. Comp Biochem Physiol C Pharmacol Toxicol Endocrinol. 113 67-71. 

MORAis M B, FESTE A, MILLER R G, LiFSCHiTZ c H (1996) Effect of resistant and digestible starch on intestinal absorption of calcium, iron, and zinc in infant pigs. Pediatr Res. 39 872-6. 

VAUGELADE P, HOEBLER C, BERNARD F, GUILLON F, LAHAYE M, DUEE P H, DARCY-VRILLON B (2000) Non-Starch polysaccharides extracted from seaweed can modulate intestinal absorption of glucose and insulin response in the pig. Reprod Nutr Dev. 40 33-47. 

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. 

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