After oral administration, the majority of drug molecules are
absorbed across the small intestine and enter the systemic
circulation via the portal vein and the liver. For some highly
lipophilic drugs (typically log PN5, lipid solubility 50 mg/g),
however, association with lymph lipoproteins in the enterocyte
leads to transport to the systemic circulation via the intestinal
lymph. The attendant delivery benefits associated with lymphatic
drug transport include a reduction in first pass metabolism and
lymphatic exposure to drug concentrations orders of magnitude
higher than that attained in systemic blood. In the current review
we briefly describe the mechanisms by which drug molecules access
the lymph and the formulation strategies that may be utilised to
enhance lymphatic drug transport. Specific focus is directed toward
recent advances in understanding regarding the impact of lipid
source (both endogenous and exogenous) and intracellular lipid
trafficking pathways on lymphatic drug transport and enterocyte
based first pass metabolism.
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