Enterohepatic circulation: physiological, pharmacokinetic and clinical implications.

摘要: Enterohepatic recycling occurs by biliary excretion and intestinal reabsorption of a solute, sometimes with hepatic conjugation deconjugation. Cycling is often associated multiple peaks longer apparent half-life in plasma concentration-time profile. Factors affecting include drug characteristics (chemical structure, polarity molecular size), transport across sinusoidal membrane canniculae membranes, biotransformation possible from intrahepatic bile ductules. Intestinal to complete the enterohepatic cycle may depend on hydrolysis conjugate gut bacteria. Bioavailability also affected extent absorption, gut-wall P-glycoprotein efflux metabolism. Recently, there has been considerable increase our understanding role transporters, gene expression enzymes, zonation. Drugs, disease genetics result induced or inhibited activity transporters metabolising enzymes. Reduced one transporter, for example canalicular multidrug resistance-associated protein (MRP) 2, enhanced others, usually quiescent basolateral MRP3, limit toxicity. In addition, physiologically relevant pharmacokinetic models, which describe recirculation terms its determinants (such as sporadic gall bladder emptying), have developed. general, prolong pharmacological effect certain drugs metabolites. Of particular importance potential amplifying variability defining differences bioavailability, volume distribution clearance given compound. Genetic abnormalities, states, orally administered adsorbents coadministered all affect recycling.