Luminal metabolism

Efflux systems and presystemic metabolism are, beside other reasons, responsible for low bioavailability of orally administered drugs. Presystemic metabolism itself can be divided into three subtypes luminal metabolism, first-pass intestinal metabolism, and first-pass hepatic... 

The pathophysiology and clinical setting of the blind-loop syndrome have been reviewed recently by Donaldson (30). It is clear that a resident bacterial flora in the proximal small intestine has a major role in the development of the absorptive and luminal defects which have been observed repeatedly in these patients (20,31-35), who have a variety of basic illness, and in experimental animals (31,36) in which an antiperistaltic pouch has been constructed either in the proximal or middle jejunum. However, the presence and extent of the absorptive defects, i.e., vitamin B12, folate, xylose, and lipid, as well as the extent of luminal metabolic alteration of bile salts have varied in individual patients. This variability is probably related to... 

The role of lipids on absorption has been extensively reviewed by Porter and Charman [29, 30]. The influences are diverse and include effects on luminal drug solubility, altering the metabolic and barrier function of the intestinal wall, stimulating lymphatic transport and a reduction in gastric transit, thereby increasing the time available for dissolution. 

Rees, J.F. and F. Baguet. 1989. Metabolic control of luminescence in the luminous organs of the teleost Porichthys effects of the metabolic inhibitors iodoacetic acid and potassium cyanide. Jour. Exper. Biol. 143 347-357. 

Dressman et al. [13] developed a dimensionless absorption potential (AP) model based on the concept that the fraction of dose absorbed, assuming negligible luminal instability and first-pass metabolism, is a function of drug lipophilicity (log P0/w), solubility (Sw), and dose (D), as defined in Eq. 2.7. 

In situ models are to evaluate absorption or membrane permeability under the physiologically relevant tissue condition. While the luminal environment can be modulated by the administered solution, the tissue condition is physiologically controlled. The estimated membrane permeability can be, in most cases, assumed to represent the transport across the epithelial cell layer at steady state or quasisteady state. However, one needs to be aware that the involvement of metabolic degradation, which may occur at the cellular surface or within the cytosol, can be a factor leading to biased estimates of membrane permeability and erroneous interpretation of the transport process. Particularly,... 

Intestinal Metabolism Intestinal drug metabolism can occur by microflora present in the gut lumen, as well as by enzymes present in luminal fluids and in the intestinal mucosa [166], Metabolism of xenobiotics by gut microflora is low in comparison to metabolism by the gut mucosa and liver [62], However, the intestinal microflora (e.g., Bacteroides and Bifidobacteria) may play an important role in the first-pass metabolism of compounds that are poorly or incompletely absorbed by the gut mucosa, especially in the lower parts of the intestine. This bacterial metabolism is largely degradative,... 

Isolated capillaries have been used for a long time to study transport and metabolic function of the blood-brain barrier [61, 72, 75, 76, 78, 87-91], In contrast to monolayer cell cultures, which are susceptible to induction or inhibition of carrier protein expression, experiments with freshly isolated capillaries directly reflect the situation at the luminal side of brain capillaries. 

Lipoprotein (LPLase) is required for the metabolism of both chylomicrons and VLDL. This enzyme is induced by insulin and transported to the luminal surface of capillary endothelium where it is in direct contact with the blood. Lipoprotein lipase hydrolyzes the fiitty adds from triglycerides carried by ch)4oinicrons and VLDL and is activated by apoC-II. 

Importantly, knowledge of intestinal bile acid transport and metabolism, coupled with increased understanding of the mechanistic basis of the pro-tumorigenic activity of bile acids against CRC cells in vitro, has recently led to development and testing of bile acid-based treatment and prevention strategies for sporadic and inflammatory bowel-disease-associated CRC. Existing evidence that manipulation of the luminal secondary bile acid pool and/or therapy with ursodeoxycholic acid (UDCA) may have promise for prevention of CRC will be assessed. 

Of the dichloroacetamides diloxanide furoate, clefamide, teclozan and etofamide the most frequently used agent is diloxanide furoate. It is the luminal amoebicide of choice in chronic intestinal amoebiasis, however it lacks efficacy acute intestinal amoebiasis. Its mechanism of action is unknown. Given orally, diloxanide is formed by bacterial hydrolases. Diloxanide is for 90% absorbed and then metabolized to diloxanide glucuronide. The remaining 10% remains in the intestine as the active drug. Diloxanide is generally well tolerated. Adverse effects include flatulence, nausea and abdominal cramps. 

Excreted primarily in the heart by the left ventricle. Metabolized by the natriuretic neutral endopeptidase enzymes on the vascular luminal surface. Half-life 18-23 min. 

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