Intestine fluids

Major gastrointestinal effects include decreased gut motility and changes in secretion of gastric and intestinal fluids. Morphine and most p receptor agonists cause pupillary constriction. Some tolerance to this effect may develop, but addicts with high opioid levels will still have miosis. Respiratory depression is the usual cause of death from opioid overdose. 

FaSSIF fasted-state simulated artificial intestinal fluid... 

Lubiprostone (Amitiza), a bicyclic acid oral agent, is approved for treatment of chronic idiopathic constipation in adults. It has not been studied in children. Lubiprostone acts locally on intestinal chloride channels and increases intestinal fluid secretion, resulting in increased intestinal motility and thereby increasing the passage of stool.6... 

Figure 5. Enzymatic degradation of H214/03 in simulated intestinal fluid. S(t)/S(0) is the fraction of remaining peptide at time t. The compositions of the samples are listed in Table HI.

A complication here, however, is noted with those drugs that exhibit a limited chemical stability in either acidic or alkaline fluids. Since the rate and extent of degradation is directly dependent on the concentration of drug in solution, an attempt is often made to retard dissolution in the fluid where degradation is seen. There are preparations of various salts or esters of drugs (e.g., erythromycin) that do not dissolve in gastric fluid and thus are not degraded there but which dissolve in intestinal fluid prior to absorption. A wide variety of chemical derivatives are used for such purposes. 

Highly insoluble molecules are in part transported in the GIT by partitioning into the mixed micelles injected into the lumen from the biliary duct in the duodenum (Fig. 2.3). Mixed micelles consist of a 4 1 mixture of bile salts and phospholipids (Fig. 7.13). In contrast, at the point of absorption in the BBB, highly insoluble molecules are transported by serum proteins. This distinction is expected to be important in in vitro assay modeling. The use of simulated intestinal fluids is appealing. 

Solubility and dissolution are processes that take place in the gastric and the luminal fluids, not on the surface of epithelial cells. Measurement of solubility ideally needs to take place at pH 1.7 (stomach) and pH 5-8 (small intestinal tract). Ideally, the screen media should resemble intestinal fluids and contain bile acid-lecithin mixed micelles. Fast and reliable techniques for assessing solubility in... 

The BCS scheme can be made more useful by incorporating a further improved basis of physicochemical profiling. For example, the role of pH in permeability measurements could be better defined. The use of simulated intestinal fluids for solubility measurements could be better promoted. The effects of fed/fasted states on absorption could be better address, in methods that have optimum clinical relevance. 

MJ Welsh, PL Smith, M Fromm, RA Frizzell. Crypts are the site of intestinal fluid and electrolyte secretion. Science 218 1219-1221, 1982. 

Castro, G.A., Hessel, J.J. and Whalen, G. (1979) Altered intestinal fluid movement in response to Trichinella spiralis in immunized rats. Parasite Immunology 1, 259-266. 

Here, APsuv is the absorption potential measured from the distribution in small unilamellar vesicles (SUV) at pH 6.8, the solubility was measured at pH 6.8 in simulated intestinal fluid, V is the volume of intestinal fluid, and dose is a mean single oral dose. Liposome partitioning is only partly correlated with octanol/water distribution. 

P. E. Luner, D. V. Kamp. Wetting behavior of bile salt-lipid dispersions and dissolution media patterned after intestinal fluids. J. Pharm. Sci. 2001,... 

Lundgren O 5-Hydroxytryptamine, enterotox-ins, and intestinal fluid secretion. Gastroenterology 1998,115 1009-1012. 

Poorly absorbed substances retain intestinal fluids, resulting in osmotic diarrhea. 

Fu, T.J., Abbott, U. And Hatzos, C., Digestibility of food allergens and non-allergenic proteins in simulated gastric and intestinal fluids — a comparative study. J. Agric. Food Chem., 50, 7154, 2002. 

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