Influence of the Lipid Dose

The amount of lipid contained in a formulation will influence drug absorption primarily via solubilization in the GIT and potentially, through activation of GI lipid digestion resulting in increased secretion of pancreatic juice and bile. Although the minimum lipid quantity required to activate lipid digestion has not been fully elucidated, oral administration of the poorly soluble antimalarial drug, halo-fantrine, to dogs in a small, pharmaceutically relevant lipid volume [0.3 g of long chain triglycerides (LCT) or mixed long chain mono- and diacylglycerols], triggered the processes of GI lipid digestion and lymphatic drug transport (24). In another study in which conscious, restrained rats received single oral doses of benzo(a)pyrene administered as a solution in 50 or 500 ^mol olive oil, the lipid volume had no effect on benzo(a)pyrene bioavailability (25).

These findings are far from conclusive but suggest that the formulator should consider the impact of any lipid-based formulation on the lipid digestion processes, particularly when multiple dosage units of a lipid-based formulation are administered as a single dose, which is common for many anti-HIV drugs.

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