Influence of the type of surfactant and the degree of dispersion on the lymphatic transport of halofantrine in conscious rats.
OBJECTIVE
To compare the lymphatic transport and the portal absorption of halofantrine (Hf) when administered in (i) a triacylglycerol (TG) solution, (ii) an o/w-emulsion that contains a metabolizable surfactant, and (iii) an o/w-emulsion that contains a synthetic surfactant.


METHODS
Lymph cannulated rats were orally dosed with Hf in a TG solution or in o/w-emulsions dispersed by lecithin or Cremophor RH40. Lymph was continuously collected, and blood was sampled periodically in the course of 30 h. Hf in the lymph and blood and TG and phosphatidyl choline (PC) in the lymph were analyzed.


RESULTS
A significantly (p < 0.05) higher level of Hf was found in the intestinal lymph when dosed in one of the emulsions (22.8+/-2.8% and 20.2+/-2.5%) compared to in the TG solution (7.9+/-1.1%). No difference in the lymphatic transport of Hf was observed between the two emulsions. The portal absorption of Hf was similar for the three vehicles.


CONCLUSIONS
The emulsified vehicles favor an increased lymphatic transport of Hf. The portal transport of Hf was not significantly different for the three vehicles. This indicates that a different degree of dispersion of the TG vehicle can change the route of transportation of Hf.
Karpf
Ditte M
DM
Department of Pharmaceutics, The Danish University of Pharmaceutical Sciences, Copenhagen, Denmark.
Holm
René
R
Kristensen
Henning G
HG
Müllertz
Anette
A
D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D001692:Biological Transport / Q000187:drug effects; D016503:Drug Delivery Systems; D004655:Emulsions; D007275:Injections, Intravenous; D007413:Intestinal Mucosa / Q000378:metabolism; D008196:Lymph / Q000187:drug effects / Q000378:metabolism; D008208:Lymphatic System / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D010616:Phenanthrenes / Q000008:administration & dosage* / Q000032:analysis / Q000493:pharmacokinetics*; D010713:Phosphatidylcholines; D011092:Polyethylene Glycols; D051381:Rats; D017207:Rats, Sprague-Dawley; D013501:Surface-Active Agents / Q000737:chemistry / Q000494:pharmacology*; D014280:Triglycerides
D004655:Emulsions; D010616:Phenanthrenes; D010713:Phosphatidylcholines; D013501:Surface-Active Agents; D014280:Triglycerides; C022131:cremophor; D011092:Polyethylene Glycols; C023768:halofantrine