Drug absorption physiological factors affecting

Orally administered dosage forms are absorbed into the systemic circulation following dissolution in the GI tract. Because substances must be in solution for the absorption from the GI lumen, the absorption rate of poorly water-soluble drugs is limited by their rate of dissolution. The dissolution rate is affected by the unique physicochemical properties of the drug and by physiological factors the pH, composition, and hydrodynamics of the GI medium. 

In relation to systemic absorption of drugs, absorption in the lung can be described as the passage of a series of barriers by the drug in order to enter the systemic circulation. It is important to realize that physiological conditions in the lung differ widely from site to site. Major physiological factors that affect pulmonary absorption are [10] ... 

Absorption from the Gl tract is governed by many factors. Broadly, it can be categorized into three classes physicochemical properties, biopharmaceutical factors, and physiological and pathophysiological factors (Mojaverian et al., 1985,1988 Nomeiretal., 1996). Since this chapter focuses on the pharmacokinetic perspectives, the main factors that could affect drug absorption are merely listed below, and will be discussed in detail in other chapters. 

Many physiological aspects affect drug absorption from the rectum (Table 7.1). Influential factors include the pH of the rectal contents, state of the mucus layer, volume and viscosity of rectal fluid, luminal pressure from the rectal wall on the dosage form, enzymatic and microbacterial degradation by rectal epithelium, presence of stools, and venous drainage differences within the rectosigmoid regions. 

The factors that affect absorption from the colon are given in Table 1. Colon-specific drug delivery is primarily dependent on two physiological factors. These are the pH level and the transit time. 

Absorption from the rectum depends on various physiological factors such as surface area, blood supply, pH, fluid volume, and possible metabolism by microorganisms in the rectum. The rectum is perfused by the inferior and middle rectal arteries, whereas the superior, the middle, and the inferior rectal veins drain the rectum. The latter two are directly connected to the systemic circulation the superior rectal vein drains into the portal system. Drugs absorbed from the lower rectum are carried directly into the systemic circulation, whereas drugs absorbed from the upper rectum are subjected to hepatic first-pass effect. Therefore, a high-clearance drug should be more bioavailable after rectal than oral administration. The volume of fluid in the rectum, the pH of that fluid, and the presence of stool in the rectal vault may affect drug absorption. Because the fluid volume is... 

Figure 9.10 Schematic representation of enterohepatic recycling (B), and a detailed view of the factors affecting drug absorption from the intestine (A). Reprinted from Clinical Pharmacokinetics, Volume 41, M.S. Roberts, B.M. Magnusson, F.J. Burczynski, and M. Weiss, Enterohepatic circulation Physiological, pharmacokinetic and clinical implications, pp. 751-790, Copyright 2002, with permission from Adis.

The rate and extent of intestinal permeation is dependent on the physicochemical properties of the compound (see Sections 16.1.2 and 16.4.3) and the physiological factors. Drugs are mainly absorbed in the small intestine due to its much larger surface area and less tight epithelium in comparison to the colon [17]. The permeation of the intestine may be affected by the presence of an aqueous boundary layer and mucus adjacent to cells, but for a majority of substances the epithelial barrier is the most important barrier to drug absorption. The lipoidal cell membrane restricts the permeability of hydrophilic and charged compounds, whereas large molecules are restricted by the ordered structure of the lipid bilayer. 

Many studies have been carried out since the late 1980s in attempts to correlate in vitro dissolution with in vivo performance. Some studies have found a significant correlation whereas others have been unsuccessful. This limited success in establishing a quantitative correlation is attributed to the fact that absorption is a complicated process. Physiological factors such as gastric emptying time, metabolism of drug by gut wall enzymes or intestinal microflora, and the hepatic first-pass effect can affect the absorption process. 

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