Absorption of drug

Whatever the route of administration, a drug must reach its site of action. In order to do this, the drug will have to cross several cell membranes to reach the blood (unless it is injected intravenously). 

The three ways by which substances, including drugs, can cross cell membranes are simple diffusion, facilitated diffusion and active transport. 

Diffusion is the mechanism by which the vast majority of drugs pass across cell membranes. Both simple diffusion and facilitated diffusion are passive processes in that no energy is required other than the kinetic energy of the molecules themselves. 

Several factors are known to influence the diffusion of substances across the cell membrane  

In practice, there is a concentration gradient because the drug is given in sufficient dose, most drug molecules are small enough to be absorbed (otherwise, they would be of no use) and the surface area and distance of the absorbing membrane are favourable. 

The various lipoid barriers of the gastrointestinal tract, the kidney tubules, and the central nervous system (CNS) allow the absorption of essential nutrients, guard against the uncontrollable disposal of electrolytes and other substances, and prevent the entrance of potentially toxic materials. 

To reach its site of action (the receptor), a drug may have to traverse a succession of membranes. For example, phenytoin, when administered orally, must cross the gastrointestinal epithelium, the blood-brain barrier, the plasma membrane, and finally the membranes of subcellular organelles of 

Multiple physical and chemical factors influence the rate and extent of absorption of drugs. These include the following  

The degree of ionization under physiologic conditions Product formulation characteristics Disintegration and dissolution rates for solid dosages Drug release characteristics for timed-release preparations Patient factors 

The surface area available for absorption Gastric and duodenal pH The gastric emptying time Bile salt pool size 

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Figure 5,4 Pharmacokinetics. The absorption distribution and fate of drugs in the body. Routes of administration are shown on the left, excretion in the urine and faeces on the right. Drugs taken orally are absorbed from the stomach and intestine and must first pass through the portal circulation and liver where they may be metabolised. In the plasma much drug is bound to protein and only that which is free can pass through the capillaries and into tissue and organs. To cross the blood brain barrier, however, drugs have to be in an unionised lipid-soluble (lipophilic) form. This is also essential for the absorption of drugs from the intestine and their reabsorption in the kidney tubule. See text for further details...

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]. 

Palm, K., Stenberg, P., Luthmann, K., Artursson, P. Polar molecular surface properties predict the intestinal absorption of drugs in humans. Pharm. Res. 1997, 14, 568-571. 

The location of the tip of the feeding tube is important when considering medication administration down a feeding tube. This is particularly true if the medication acts locally in the GI tract itself. For example, sucralfate and antacids act locally in the stomach. Therefore, administration of these medications through a duodenal or jejunal tube is not logical. Likewise, for medications such as itraconazole that require acid for best absorption, administration directly into the duodenum or jejunum would be expected to result in suboptimal absorption. Absorption of drugs when administered directly into the small bowel, especially the jejunum, rather than into the stomach is another area where more research would be useful. 

Table Da. Percent Absorption of Drugs by Polyacid Resins [50 mg agent/gram resin]...

Drugs in Class III have good aqueous solubility but poor membrane permeability (e.g., bidisomide, bispho-sphonates, captopril, and furosemide). Food and food components would only be expected to influence absorption of drugs in this class if they affected some aspect... 

LS Schanker. Absorption of drugs from the rat colon. J Pharmacol Exp Ther 126 283-290, 1959. 

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

LF Prescott. Gastrointestinal absorption of drugs. Med Clin North Am 58 907-916, 1974. 

Fig. 8 Factors affecting the rate of absorption of drug from the gastrointestinal tract. (From Ref. 15.). 

These animal studies should indicate to the pharmacist that blood flow can, under certain circumstances, be an important patient variable that may affect the absorption of drugs. Patients in heart failure would generally be expected to have a decreased cardiac output and, therefore, a decreased splanchnic blood flow. This could lead to a decreased rate of absorption for drugs when the blood flow rates in Eq. (7) become rate-limiting. In addition, redistribution of cardiac output during cardiac failure may lead to splanchnic vasoconstriction in patients [57], Other disease states and physical activity can also decrease blood flow to the GIT [2 4], Thus, the pharmacist must be aware of the possible effect of blood flow rate, especially alterations in the rate, on the availability of drugs. 

L. Z. Benet, A. Greither, and W. Meister, Gastrointestinal absorption of drugs in patients with cardiac failure, in The Effect of Disease States on Drug Pharmacokinetics (L. Z. Benet, ed.), Academy of Pharmaceutical Association, Washington, D.C, 1976, pp. 33-50. 

The absorption of drugs from the rectal [32] cavity has been studied in some detail. Muranishi et al. [34] have shown that a significant increase in the absorption and lymphatic uptake of soluble and colloidal macromolecules can be achieved by pretreating the rectal mucosal membrane with lipid-nonionic surfactant mixed micelles. They found no evidence of serious damage of the mucosal membrane. Davis [30] suggested that the vaginal cavity could be an effective delivery site for certain pharmaceuticals, such as calcitonin, used for the treatment of postmenopausal osteoporosis. 

The properties of the human GIT that are relevant to the absorption of drug products have been collected from several sources [62-69]. Figure 2.3 shows a cartoon of the GIT, indicating surface area and pH (fasted and fed state) in the various... 

FGJ Poelma, R Breas, JJ Tukker. Intestinal absorption of drugs. IV. The influence of taurocholate and L-cysteine on the barrier function of mucus. Int J Pharm 64 161-169, 1990. 

Lee [203] developed such approximate solutions for spheres, cylinders, and slabs. For absorption of drug by a flat sheet, the equations used are... 

Sugawara, M., Takekuma, Y., Yamada, H., Kobayashi, M., Iseki, K., Miyazaki, K., A general approach for the prediction of the intestinal absorption of drugs regression analysis using the physicochemical properties and drug-membrane electrostatic interaction, J. Pharm. Sci. 1998, 87, 960-966. 

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