Comparison of total oral bioavailability and the lymphatic transport of halofantrine from three different unsaturated triglycerides in lymph-cannulated conscious rats.
The lymphatic transport and the portal absorption of the lipophilic drug halofantrine were investigated in a conscious rat model. The rats were dosed with 0.1 g with triolein, trilinolein or trilinolenin containing 2 mg halofantrine. Following oral administration of the triglycerides, the mesenteric lymph and plasma samples were collected. The lymphatic transport for halofantrine was 11.1+/-1.2 after administration of trilinolein, 9.0+/-3.5 for trilinolenin and 8.6+/-2.2 for triolein and the total amount of halofantrine transported in the lymph was linear proportional with the amount of triglyceride in the lymph. The absorption of halofantrine directly into the blood showed a trend towards a higher AUC for trilinolien and trilinolenin compared to triolein, but no statistical difference could be found. The statistically analysis of the mean total bioavailability therefore shows that the absorption of halofantrine was largely independent on triglyceride unsaturation.
Holm
R
R
Department of Pharmaceutics, The Royal Danish School of Pharmacy, Universitetsparken 2, DK-2100 Copenhagen, Denmark.
Müllertz
A
A
Christensen
E
E
Høy
C E
CE
Kristensen
H G
HG
D000284:Administration, Oral; D000818:Animals; D000962:Antimalarials / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D001682:Biological Availability; D001693:Biological Transport, Active; D002404:Catheterization / Q000379:methods; D003243:Consciousness / Q000502:physiology; D005224:Fats, Unsaturated / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008208:Lymphatic System / Q000378:metabolism*; D008297:Male; D010616:Phenanthrenes / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014280:Triglycerides / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*
D000962:Antimalarials; D005224:Fats, Unsaturated; D010616:Phenanthrenes; D014280:Triglycerides; C023768:halofantrine