Role of the lymphatics in the intestinal absorption and distribution of drugs.

mesenteric lymph collected after intraduodenal administration of p-aminosahicylic acid (PAS) contained relatively more unmetabolized PAS than did thoracic lymph or plasma sampled after either duodenal or i.v. administration, indicating direct absorption of the drug via the lymphatic system. That tetracycline also can be absorbed directly into intestinal lymph was demonstrated histologically by the appearance of fluorescence in the central lacteals only in the intestinal area containing the drug. However, under normal conditions. the lymphatic route accounted for only a small percentage of the total absorption of the two drugs chosen as models. The difference in absorption potential between lymph and blood capillaries is related to differences in rates of flow within the two circulatory systems. Increasing lymph flow by oral administration of the lymphogogue, tripalmitin, increased the quantities of both drugs absorbed via intestinal lymph. Decreasing intestinal blood flow by ligation of the superior mesenteric vein increased the proportion of PAS absorbed through the lymphatics. After i.v. administration of PAS, the concentrations of both free and total PAS were the same in plasma and lymph even though PAS is bound to plasma protein. The concentration of tetracycline was 5 times higher in lymph than in blood 10 minutes after its i.v. administration and did not equal that in blood until 90 minutes. This may have importance in the treatment of diseases associated with the lymphatic system.