Intestinal lymphatic transport of halofantrine occurs after oral administration of a unit-dose lipid-based formulation to fasted dogs.
OBJECTIVE
To examine whether the small quantities of lipid present in unit-dose microemulsion formulations comprising medium- (C8-10) or long-chain (C18) glyceride lipids can stimulate the intestinal lymphatic transport of halofantrine (Hf), a model lymphatically transported drug.


METHODS
Hf (50 mg) was administered to thoracic lymph duct- and cephalic vein-cannulated fasted greyhound dogs. Drug was formulated as a single soft gelatin capsule containing approximately 1 g of a microemulsion preconcentrate based on either medium- or long-chain glycerides. Thoracic lymph was collected, and systemic plasma samples taken over 10 h postdose.


RESULTS
The extent of lymphatic transport of Hf after administration of the long-chain lipid formulation was high (28.3% of dose), and significantly higher than that seen after administration of the medium-chain formulation (5.0% of dose). Plasma levels of Hf were not significantly different across the two formulations when assessed by AUC0-10h.


CONCLUSIONS
This is the first study to demonstrate that the small amounts of lipid present within a single lipid-based dose form can support substantial intestinal lymphatic transport in the fasted state. Furthermore, microemulsions based on long-chain glycerides appear to be more effective with respect to lymphatic transport than the equivalent medium-chain formulation.
Khoo
Shui-Mei
SM
Department of Pharmaceutics, Victorian College of Pharmacy, Monash University, Parkville, Victoria 3052, Australia.
Shackleford
David M
DM
Porter
Christopher J H
CJ
Edwards
Glenn A
GA
Charman
William N
WN
D000042:Absorption; D000284:Administration, Oral; D000818:Animals; D001692:Biological Transport; D002626:Chemistry, Pharmaceutical; D004285:Dogs; D004337:Drug Carriers; D004655:Emulsions; D005215:Fasting; D007413:Intestinal Mucosa / Q000378:metabolism*; D008055:Lipids / Q000737:chemistry / Q000494:pharmacology*; D008208:Lymphatic System / Q000378:metabolism*; D010616:Phenanthrenes / Q000097:blood / Q000493:pharmacokinetics*; D013997:Time Factors
D004337:Drug Carriers; D004655:Emulsions; D008055:Lipids; D010616:Phenanthrenes; C023768:halofantrine