TY - JOUR T1 - The influence of diffusional barriers on presystemic gut elimination. JF - Drug Metabolism and Disposition JO - Drug Metab Dispos SP - 521 LP - 526 VL - 16 IS - 4 AU - P R Gwilt AU - S Comer AU - P R Chaturvedi AU - D H Waters Y1 - 1988/07/01 UR - http://dmd.aspetjournals.org/content/16/4/521.abstract N2 - A number of drugs undergo biotransformation in the gut wall or lumen. In many cases drug extraction is greater after oral administration compared with parenteral administration. This may indicate that the diffusional clearance of drug across the blood-mucosa interface is less than that across the lumen-mucosa interface. The consequence of diffusional barriers in the gut on presystemic gut elimination (PGE) have been investigated by computer simulation of a physiological pharmacokinetic model. The following was found regarding a diffusional barrier of the blood-mucosa interface: 1) it enhances PGE, 2) it invalidates certain pharmacokinetic methods to assess PGE, 3) it makes PGE sensitive to changes in drug binding in the blood, and 4) if the diffusional barrier exists for the generated metabolite but not for the drug, methods to assess drug absorption by comparing area under the curve relationships of the metabolite after oral and iv drug administration are inaccurate. ER -