INFLUENCE OF ROUTE OF ADMINISTRATION ON AREA UNDER PLASMA CONCENTRATION-TIME CURVE

The so‐called law of corresponding areas has been used to assess the percent of absorption by comparison of the relative areas under the plasma concentration‐time curves after oral and intravenous administration. These analyses are based on the presumption that the resultant areas are independent of the route of administration. After oral administration, every absorbed molecule must pass through the gut wall and when absorbed via the hepatic portal system must traverse through the liver, before reaching the central compartment, from which samples are obtained for analysis. However, after the usual i.v. administration, less than 30% of the molecules traverse through the liver in the first circulatory pass. Therefore, if a significant degree of metabolism takes place in the gut or in the liver, the resultant areas will not be identical. This has been verified in dogs by comparison of areas after infusion of acetylsalicylic acid by the vena cava, by the hepatic portal vein, and after oral administration. The data obtained with acetylsalicylic acid indicate metabolism occurs in both the gut wall and in the liver, thereby causing a large reduction in the areas obtained after oral dosing or hepatic portal vein infusion when compared to the area obtained after infusion by the vena cava. Copyright © 1969 Wiley‐Liss, Inc., A Wiley Company