ABSTRACT
The lymphatic route has been suggested as a method of by-passing first-pass metabolism for extremely lipid soluble drugs. It has been argued that lipophilic drugs may become incorporated into lipid micelles and transformed into chylomicrons by the epithelium before being released into the lymphatic circulation. All the lymph from the lower part of the body flows up through the thoracic duct and empties into the venous system of the left internal jugular vein, thus avoiding the hepatic portal system. In order to be transported in the chylomicrons, the drug must be extremely lipophilic. The ratio of portal blood flow to intestinal lymph flow in the rat is approximately 500:1. Although lymph is the major transport route for fats, it only contains 1% lipids. The overall effect is to make systemic absorption 50,000 times more efficient than lymphatic absorption. In order for a drug to be transported at equal rates by both lymphatic and systemic circulations, the drug must be 50,000 times more soluble in the chylomicrons than the plasma, i.e have a partition coefficient of 50,000 (log P=4.7)94.
