Structured triglyceride vehicles for oral delivery of halofantrine: examination of intestinal lymphatic transport and bioavailability in conscious rats.
OBJECTIVE
To compare the influence of triglyceride vehicle intramolecular structure on the intestinal lymphatic transport and systemic absorption of halofantrine in conscious rats.


METHODS
Conscious, lymph cannulated and nonlymph cannulated rats were dosed orally with three structurally different triglycerides; sunflower oil, and two structured triglycerides containing different proportion and position of medium-(M) and long-chain (L) fatty acids on the glycerol backbone. The two structured triglycerides were abbreviated MLM and LML to reflect the structural position on the glycerol. The concentration of halofantrine in blood and lymph samples was analyzed by HPLC.


RESULTS
Both the lymphatic transport and the total absorption of halofantrine were enhanced by the use the MLM triglyceride. The estimated total absorption of halofantrine in the lymph cannulated animals was higher than in the nonlymph cannulated animals, and this was most pronounced for the animals dosed with the structured triglycerides.


CONCLUSIONS
Using MLM as vehicle increases the portal absorption of halofantrine and results in similar lymphatic transport levels when compared to sunflower oil. Total absorption when assessed as absorption in the blood plus lymphatic transport for halofantrine after administration in the MLM triglyceride was higher than after administration in sunflower oil.
Holm
René
R
Department of Pharmaceutics, The Royal Danish School of Pharmacy, Copenhagen, Denmark.
Porter
Christopher J H
CJ
Müllertz
Anette
A
Kristensen
Henning G
HG
Charman
William N
WN
D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D016503:Drug Delivery Systems / Q000379:methods*; D007413:Intestinal Mucosa / Q000378:metabolism*; D008196:Lymph / Q000378:metabolism*; D008208:Lymphatic System / Q000378:metabolism; D014677:Pharmaceutical Vehicles; D010616:Phenanthrenes / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D051381:Rats; D014280:Triglycerides / Q000008:administration & dosage / Q000493:pharmacokinetics*
D014677:Pharmaceutical Vehicles; D010616:Phenanthrenes; D014280:Triglycerides; C023768:halofantrine