Influence of bile on the absorption of halofantrine from lipid-based formulations

The bioavailability of the poorly soluble model drug halofantrine, dosed in a soy bean oil solution or in a self-nanoemulsifying drug delivery system (SNEDDS), at two levels of lipid, was assessed in rats. Three rat models were used: intact rats, sham-operated rats and bile duct cannulated rats. The study showed no difference in the pharmacokinetic parameters between intact and sham-operated rats. Tmax increased with lipid load for both oil solution and SNEDDS, whereas Cmax and the absolute bioavailability were significantly higher for the SNEDDS at both lipid dosing levels. Bile duct cannulation of the rats reduced the Cmax and the absolute bioavailability of halofantrine significantly, by a factor of 2, for all 4 treatments. These data clearly demonstrate that bile has an importance for the absorption of drugs from lipid-based formulations independent of the type.

Graphical abstractPlacement of a cannula in the bile duct close to the liver enables investigation of how bile affects the absorption of low soluble compounds from lipid-based formulations without removing the pancreatic co-lipase dependent lipase.Figure optionsDownload full-size imageDownload high-quality image (120 K)Download as PowerPoint slide