CIRCULACION ENTEROHEPATICA PDF

Las sales biliares primarias, derivadas de los acidos colico y desoxicolico, se sintetizan en el higado a partir del colesterol y luego se conjugan con la glicina o la taurina dentro del hepatocito. Una vez secretados en el intestino, los acidos biliares primarios son modificados por las bacterias intestinales que forman los acidos biliares secundarios desoxicolico y litocolico. Solo una pequena fraccion es vertida a la circulacion general, debido a la eficiencia de la extraccion hepatica los valores plasmaticos de los acidos biliares son bajos. Tras la extraccion hepatica, los acidos biliares vuelven a circular por los canaliculos y regresan a la via biliar, completandose el circuito. Una pequena cantidad de acidos biliares intestinales no llega a absorberse por el sistema porta, sino que se excreta con las heces.

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Enterohepatic circulation: physiological, pharmacokinetic and clinical implications. Cycling is often associated with multiple peaks and a longer apparent half-life in a plasma concentration-time profile. Factors affecting biliary excretion include drug characteristics chemical structure, polarity and molecular size , transport across sinusoidal plasma membrane and canniculae membranes, biotransformation and possible reabsorption from intrahepatic bile ductules. Intestinal reabsorption to complete the enterohepatic cycle may depend on hydrolysis of a drug conjugate by gut bacteria.

Bioavailability is also affected by the extent of intestinal absorption, gut-wall P-glycoprotein efflux and gut-wall metabolism. Recently, there has been a considerable increase in our understanding of the role of transporters, of gene expression of intestinal and hepatic enzymes, and of hepatic zonation. Drugs, disease and genetics may result in induced or inhibited activity of transporters and metabolising enzymes.

Reduced expression of one transporter, for example hepatic canalicular multidrug resistance-associated protein MRP 2, is often associated with enhanced expression of others, for example the usually quiescent basolateral efflux MRP3, to limit hepatic toxicity.

In addition, physiologically relevant pharmacokinetic models, which describe enterohepatic recirculation in terms of its determinants such as sporadic gall bladder emptying , have been developed.

In general, enterohepatic recirculation may prolong the pharmacological effect of certain drugs and drug metabolites. Of particular importance is the potential amplifying effect of enterohepatic variability in defining differences in the bioavailability, apparent volume of distribution and clearance of a given compound. Genetic abnormalities, disease states, orally administered adsorbents and certain coadministered drugs all affect enterohepatic recycling.

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