Comparison of the lymphatic transport of halofantrine administered in disperse systems containing three different unsaturated fatty acids.
OBJECTIVE
To compare the influence of the degree of fatty acid unsaturation (oleic [C18:], linoleic [C18:2], or linolenic acid [C18:3]), with the intestinal lymphatic transport of halofantrine free base from disperse systems in anesthetized rats.


METHODS
The mesenteric lymph duct was cannulated in anesthetized rats. Lipid vehicle containing halofantrine was administered by intraduodenal infusion. The concentration of halofantrine in blood and lymph samples was analyzed.


RESULTS
The rank order of the lymphatic transport of halofantrine was C18:2 > C18:1 > C18:3. Comparison of the area under the curve (AUC) from the three fatty acids showed no statistically significant differences between the AUCs from the lymph cannulated rats. In terms of rank order effects, the plasma concentrations of halofantrine were highest for the rats dosed C18:2 followed by C18:3 and C18:1.


CONCLUSIONS
Using C18:2 as a vehicle increased the lymphatic transport of halofantrine 16.6-fold over that observed for the system containing C18:3. The extent of lymphatic transport for the C18:1 system did not differ from the other two formulations, but the combined lymph and plasma data indicated that the C18:2 was the most suitable lipid vehicle for the oral delivery of halofantrine.
Holm
R
R
Department of Pharmaceutics, Royal Danish School of Pharmacy, Copenhagen.
Müllertz
A
A
Pedersen
G P
GP
Kristensen
H G
HG
D000818:Animals; D000962:Antimalarials / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D002914:Chylomicrons / Q000378:metabolism; D004655:Emulsions; D005231:Fatty Acids, Unsaturated; D007413:Intestinal Mucosa / Q000378:metabolism; D008208:Lymphatic System / Q000378:metabolism*; D010616:Phenanthrenes / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D051381:Rats; D012995:Solubility; D012996:Solutions; D014280:Triglycerides / Q000378:metabolism
D000962:Antimalarials; D002914:Chylomicrons; D004655:Emulsions; D005231:Fatty Acids, Unsaturated; D010616:Phenanthrenes; D012996:Solutions; D014280:Triglycerides; C023768:halofantrine