Effect of oily vehicles on absorption of mepitiostane by the lymphatic system in rats.
[14C]Mepitiostane in various vehicles was administered to the small intestine of anaesthetized rats with cannulated thoracic ducts, and the effect of lipids on lymphatic absorption was examined. The extent of lymphatic absorption was greatest when administered in triolein and sesame oil, which are triglycerides of long-chain fatty acids. Absorption in the presence of other vehicles was in the order of 10% Tween 80 aqueous solution greater than monolein greater than oleic acid approximately oleic acid/monolein (2:1 mol/mol) greater than aqueous suspension. Differences between the extents of lymphatic absorption of mepitiostane in the various formulations were not due to variation in the lymph flow but to the increased secretion of chylomicron and very low density lipoproteins. During absorption of mepitiostane from the small intestine, oil affected not only the penetration into epithelium cells and the metabolism in them, but also the partition between blood and lymph.
Shionogi Research Laboratories, Shionogi & Co. Ltd, Osaka, Japan.
T
T
Ichihashi
H
H
Kinoshita
Y
Y
Takagishi
H
H
Yamada
D000732:Androstanols / Q000008:administration & dosage / Q000032:analysis / Q000493:pharmacokinetics*; D000818:Animals; D002250:Carbon Radioisotopes; D004337:Drug Carriers; D005260:Female; D007408:Intestinal Absorption / Q000187:drug effects*; D007421:Intestine, Small / Q000378:metabolism; D008196:Lymph / Q000737:chemistry; D008208:Lymphatic System / Q000378:metabolism*; D009821:Oils / Q000008:administration & dosage*; D051381:Rats; D011919:Rats, Inbred Strains
D000732:Androstanols; D002250:Carbon Radioisotopes; D004337:Drug Carriers; D009821:Oils; C006242:mepitiostane