Intestinal blood flow

The rate-limiting step in the absorption of those compounds that readily penetrate the intestinal membrane (i.e., have a large permeability coefficient) may be the rate at which blood perfuses the intestine. However, absorption will be independent of blood flow for those compounds that are poorly permeable. Extensive studies have illustrated this concept in rats [106,107]. The absorption rate of tritiated water, which is rapidly absorbed from the intestine, is dependent on intestinal blood flow, but a poorly absorbed compound, such as ribitol, penetrates the intestine at a rate independent of blood flow. In between these two extremes are a variety of intermediate compounds whose absorption rate is dependent on blood flow at low flow rates but independent of blood flow at higher flow rates. By altering blood flow to the intestine of the dog, as blood flow decreased the rate of sulfaethidole absorption also decreased [108]. These relationships are illustrated in Fig. 16. 

Fig. 16 (A) Absorption rate constant of sulfaethidole in dogs as a function of mesenteric blood flow. (Based on data from Ref. 108.) (B) Absorption rate of several compounds in rats as a function of intestinal blood flow. (Based on data from Ref. 107.)...

D Winne. Formal kinetics of water and solute absorption with regard to intestinal blood flow. J Theo-ret Biol 2 1-18, 1970. 

D Winne, J Remischovsky. Intestinal blood flow and absorption of nondissociable substances. J Pharm Pharmacol 22 640-641, 1970. 

Absorption J. Intestinal blood flow Gastric pH J. Active absorption i GER J. Rate of absorption ... 

Dofetilide is 100% bioavailable. Verapamil increases peak plasma dofetilide concentration by increasing intestinal blood flow. Eighty percent of an oral dose is eliminated by the kidneys unchanged the remainder is eliminated in the urine as inactive metabolites. 

Dofetilide is 100% bioavailable. Verapamil increases peak plasma dofetilide concentration by increasing intestinal blood flow. Eighty percent of an oral dose is eliminated by the kidneys unchanged the remainder is eliminated by the kidneys as inactive metabolites. Inhibitors of the renal cation secretion mechanism, eg, cimetidine, prolong the half-life of dofetilide. Since the QT-prolonging effects and risks of ventricular proarrhythmia are directly related to plasma concentration, dofetilide dose must be based on the estimated creatinine clearance. Treatment with dofetilide should be initiated in hospital after baseline measurement of the QTc and serum electrolytes. A baseline QTC of > 450 ms (500 ms in the presence of an intraventricular conduction delay), bradycardia of < 50 beats/min, and hypokalemia are relative contraindications to its use. 

Intestinal Blood Flow. The mechanistic relationship among intestinal blood flow and absorption, secretion, and metabolic activity of the intestinal mucosa is unclear. However, there is evidence that impaired intestinal blood flow rate correlates with a decrease in drug absorption rate. It has been postulated that reduced blood flow slows down the absorption rate... 

Moneta, G.L. Taylor, D.C. Helton, W.S. Mulholland, M.W. Strandness, D.E. Duplex ultrasound measurement of postprandial intestinal blood flow Effect of meal composition. Gastroenterology 1988, 95 (5), 1294—1301. 

An active dipeptide transport system that depends on hydrogen ions takes up non-ester amino-beta-lactams (penicillin, amoxicillin, and oral first-generation cephalosporins) (337-339) and specific cephalosporins that lack the alpha-amino group (cefixime, ceftibuten, cefdinir, cef-prozil) (340,341). Nifedipine increases amoxiciUin and cefixime absorption, probably by stimulating the dipeptide transport system, since the serum concentrations of passively absorbed drugs and intestinal blood flow did not change (342-344). 

Figure 9.6 The dependence of salicylic acid absorption on the net water flux (positive sign flow directed from the lumen and towards the blood) in the rat jejunal loop perfused with hypo-, iso- and hypertonic solutions at pH 6.2 and 2.2. The lines, mean values with 95% confidence limits (shaded areas), were calculated by means of the parameters determined by a kinetic model with the following constants concentration of salicylic acid in the perfusion solution 32.3 /

Lundberg,J.M., Tatemoto, K., Terenius, L., Hellstrom, P.M., Mutt, V, Hokfelt, T. etal. (1982a) Localization of the peptide YY (PYY) in gastrointestinal endocrine cells and effects on intestinal blood flow and motility. Proc. Natl Acad. Sci. USA 79, 4471-4475. 

Maconi G, Imbesi V, Bianchi Porro G (1996) Doppler ultrasound measurement of intestinal blood flow in inflammatory bowel disease. Scand J Gastroenterol 31 590-593... 

Goitein D, et al. Microsphere intestinal blood flow analysis during pneumoperitoneum using carbon dioxide and helium. Surg Endosc Interv Tech 2005 19 541-5. 

Guan, X., B. Stoll, X. Lu, K.A. Tappenden, J.J. Holst, B. Hartmann, and D.G. Bunin, 2003. GLP-2-mediated up-regulation of intestinal blood flow and glucose uptake is nitric-oxide dependent in TPN-fed piglets. Gastroenterology 125, 136-147. 

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