title: Influence of bile on the absorption of halofantrine from lipid-based formulations.
abstract: 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. T(max) increased with lipid load for both oil solution and SNEDDS, whereas C(max) and the absolute bioavailability were significantly higher for the SNEDDS at both lipid dosing levels. Bile duct cannulation of the rats reduced the C(max) 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.
authors.affiliation: Preformulation, H Lundbeck A/S, Valby, Denmark. rhol@lundbeck.com
authors.forename: René
authors.initials: R
authors.lastname: Holm
authors.forename: Henrik
authors.initials: H
authors.lastname: Tønsberg
authors.forename: Erling B
authors.initials: EB
authors.lastname: Jørgensen
authors.forename: Puyan
authors.initials: P
authors.lastname: Abedinpour
authors.forename: Shafiq
authors.initials: S
authors.lastname: Farsad
authors.forename: Anette
authors.initials: A
authors.lastname: Müllertz
mesh_terms: D000818:Animals; D001646:Bile / Q000378:metabolism*; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical / Q000379:methods; D016503:Drug Delivery Systems / Q000379:methods; D007408:Intestinal Absorption; D008055:Lipids / Q000008:administration & dosage / Q000737:chemistry*; D008297:Male; D009821:Oils / Q000737:chemistry; D010316:Particle Size; D010616:Phenanthrenes / Q000008:administration & dosage / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013024:Soybean Oil / Q000737:chemistry
chemical_list: D008055:Lipids; D009821:Oils; D010616:Phenanthrenes; D013024:Soybean Oil; C023768:halofantrine