Intestine segments

Another relatively new lipophilicity scale proposed for use in ADME studies is based on MEKC [106]. A further variant is called BMC and uses mobile phases of Brij35 [polyoxyethylene(23)lauryl ether] [129]. Similarly, the retention factors of 16 P-blockers obtained with micellar chromatography with sodium dodecyl sulfate as micelle-forming agent correlates well with permeability coefficients in Caco-2 monolayers and apparent permeability coefficients in rat intestinal segments [130]. 

An intestine transplant may involve the use of an entire intestine or just a shortened segment. Most intestine transplants completed in the United States have involved the transplant of the full organ and often are performed in conjunction with a liver transplant. Although most intestine transplants involve organs harvested from a deceased donor, recent advances in the field now have made it possible for living-donor intestinal segment transplants. There were 178 intestinal transplant recipients (171 deceased donors, 7 living donors) in 2005.3... 

The Ph Eur test procedure for gastroresistance should be applied. Two media should be used, e.g., at pH 2 for one hour to detect possible damage to the gastroresistant coating and to detect active ingredient diffusion (with a limits of 10% release of active ingredient) and at pH 6.8 to simulate transfer to the intestinal segment (with complete release). Biostudy results should be reported to confirm acceptable in vivo performance. 

Artursson, P., Ungell, A.-L., Lofroth, J.-E., Selective paracellular permeability in two models of intestinal absorption cultured monolayers of human intestinal epithelial cells and rat intestinal segments, Pharm. Res. 1993, 30, 1123-1129. 

Jejunal Peff and other variables were calculated from the steady-state level in the perfusate leaving the intestinal segment. It has been reported previously that a well-mixed model best describes the hydrodynamics within the perfused jejunal segment, and Pejr is calculated according to Eq. (5) ... 

Drugs may also undergo hydrolysis by intestinal esterases (hydrolases), more specifically carboxylesterases (EC 3.1.1.1) in the intestinal lumen and at the brush border membrane [58, 59]. It has been shown that intestinal hydrolase activity in humans was closer to that of the rat than the dog or Caco-2 cells [60]. In these studies, six propranolol ester prodrugs and p-nitrophenylacetate were used as substrates, and the hydrolase activity found was ranked in the order human > rat Caco-2 cells > dog for intestinal microsomes. The rank order in hydrolase activity for the intestinal cytosolic fraction was rat > Caco-2 cells = human > dog. The hydrolase activity towards p-nitrophenylacetate and tenofovir disoproxil has also been reported in various intestinal segments from rats, pigs and humans. The enzyme activity in intestinal homogenates was found to be both site-specific (duodenum > jejunum > ileum > colon) and species-dependent (rat > man > Pig)-... 

Location and extent Gastric stomach Similar flora present in duodenum and proximal jejunum Small intestine, segmental or global Backwards colonization of the stomach in severe forms... 

A small bowel transit study can be used to evaluate intestinal propulsion and clearance, and the presence of Enterobacteriacea (Gram-negative bacilli) in the small bowel indicates delayed transit [111]. The wide normal variability, however, makes transit tests rather insensitive, and thus less useful clinically [126, 127], It is also a problem that accelerated and delayed transit may coexist in neuropathies and confuse the interpretation. Finally, as nutrients are mostly absorbed in the proximal small bowel, and the rate and pattern of transit vary along the intestine, segmental failure of transit is easily missed by global... 

Table 1 Mean Flow Rates (MFRs) in Various Intestinal Segments Are Related to the Phase of the MMC in Humans...

At steady state, the following mass balance can be applied across a perfused segment of the intestine. The rate of mass entering and exiting the intestinal segment (i.e. cylindrical tube) is the product of the volumetric flow rate (Q) and either inlet concentration (Cin) or outlet concentration (Cout), respectively. Assuming that mass is lost from the tube only by absorption into the blood, the mass absorbed per unit time is the difference between the rates of mass flow in and out of the tube as follows ... 

This technique, also referred to as the auto-perfused method after experiments by Windmuller and Spaeth [67] involves cannulation and drainage of a vein from an intestinal segment and donor blood replacement via a sustainable blood vessel (e.g. jugular vein). The most commonly reported site of cannulation is the mesenteric vein. Cannulation is performed as follows. A midline incision of 4 cm is made and an 8-12-cm segment of the ileum is located to... 

This theory was further explored in an anaesthetised pig model, which facilitated portal vein and bile sampling [86], However, the hepatic extraction ratio and the biliary clearance of fexofenadine were unaffected by verapamil in the pig model. The question as to why verapamil/ketoconazole increase the fraction absorbed (i.e. based on appearance kinetics) and yet the fraction absorbed estimated on the basis of disappearance kinetics (i.e. /err) for the intestinal segment appears unchanged remains to be explored and most likely reflect multiple interplay between absorptive and efflux drug transporters in the intestinal tissue. 

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