Comparison of the lymphatic transport of a lipophilic drug from vehicles containing alpha-tocopherol and/or triglycerides in rats.
The applicability of alpha-tocopherol as a lymphotropic carrier for a highly lipophilic drug has been evaluated. Transport to the intestinal lymph of the highly lipophilic model drug, Lu28-179, in rats after administration to the stomach in an alpha-tocopherol emulsion was compared with lymphatic transport after administration of a sesame oil emulsion and an alpha-tocopherol/sesame oil emulsion. Lymphatic transport of the triglycerides and of alpha-tocopherol was determined. A conscious rat model was used, and the mesenteric lymph was collected. There was no significant difference between the cumulative masses of triglyceride from the two emulsions containing triglyceride 24 h after administration. Administration of an alpha-tocopherol emulsion seemed to induce mobilization of endogenous triglyceride. The lymphatic transport of alpha-tocopherol was less than 1 mg 24 h after administration of both emulsions containing alpha-tocopherol. The absorption of Lu28-179 from the alpha-tocopherol emulsion was very low, with a lymphatic recovery of 0.05%. When administered in an alpha-tocopherol/sesame oil emulsion, the recovery of Lu28-179 increased sevenfold to 0.35%. However, after administration of Lu28-179 in a sesame oil emulsion, the lymphatic recovery increased a further 13-fold to 4.5%. In conclusion, the study showed that alpha-tocopherol did not promote lymphatic absorption of Lu28-179 and thus was not a good lymphotropic carrier, as compared with sesame oil. Alpha-tocopherol in combination with sesame oil was not a good lymphotropic carrier either. The non-absorbed alpha-tocopherol fraction in the intestine might be able to prevent the absorption of Lu28-179.
Nielsen
P B
PB
Dumex-Alpharma ApS, Copenhagen, Denmark.
Müllertz
A
A
Norling
T
T
Kristensen
H G
HG
D000284:Administration, Oral; D000818:Animals; D014151:Anti-Anxiety Agents / Q000737:chemistry / Q000493:pharmacokinetics*; D001693:Biological Transport, Active; D007211:Indoles / Q000737:chemistry / Q000493:pharmacokinetics*; D008196:Lymph / Q000378:metabolism; D008208:Lymphatic System / Q000378:metabolism; D008297:Male; D008643:Mesentery; D023421:Models, Animal; D051381:Rats; D017207:Rats, Sprague-Dawley; D012715:Sesame Oil / Q000494:pharmacology; D013141:Spiro Compounds / Q000737:chemistry / Q000493:pharmacokinetics*; D014280:Triglycerides / Q000378:metabolism / Q000493:pharmacokinetics*; D024502:alpha-Tocopherol / Q000378:metabolism / Q000493:pharmacokinetics*
D014151:Anti-Anxiety Agents; D007211:Indoles; C109644:Lu 28-179; D013141:Spiro Compounds; D014280:Triglycerides; D012715:Sesame Oil; D024502:alpha-Tocopherol