Intestinal lymphatic drug transport: an update

The trend towards identification of poorly water-soluble and highly lipophilic candidate drug molecules has led to an increase in interest in intestinal lymphatic drug transport. In this article we provide a brief background to the mechanism of access of drugs to the intestinal lymph and the role of lipid digestion and absorption in the stimulation of lymphatic transport. The ability of different lipid types to stimulate lymphatic drug transport, is addressed, concentrating specifically on the impact of the class, chain length and degree of unsaturation of co-administered lipids. Comment is also made as to the relevance of dosing different lipid volumes to the rat and the possible complications this may provide when trying to assess the likely extent of intestinal lymphatic transport. Recent studies are described in which the extent of lymphatic transport of a highly lipophilic antimalarial, halofantrine, was investigated after post-prandial administration to greyhound dogs. Finally the possible future directions for studies of intestinal lymphatic transport are discussed, including the use of cell culture models and genetically modified animals.