Hepatic uptake of lipid-soluble drugs from fat emulsion.
Oil violet in a fat emulsion was taken up into the parenchymal cells of rat liver in vitro. The uptake was greater at 37 degrees C than 25 degrees C or 4 degrees C, and it was increased by addition of postheparin plasma including lipoprotein lipase activity into the reaction medium. The uptake from the emulsion with smaller particles was greater than that from the emulsion with larger particles. The hepatic uptake of 14C-cholesteryl oleate in the emulsion by recirculating perfusion of the liver in situ was also increased by postheparin plasma in the perfusion medium. Its enhancing effect was found for distribution in the parenchymal cells but not in the Kupffer cells. The previous perfusion of Intralipos of the commercial fat emulsion reduced the hepatic uptake of 14C-cholesteryl oleate in the emulsion. The emulsion particle sizes were reduced by postheparin plasma both in vitro and in situ. Consequently, it was suggested that a lipid-soluble compound entrapped in the fat emulsion is taken up into the parenchymal cells by receptor-mediated process via the reduced particle sizes emulsion (remnant), which is a mechanism similar to the dietary fat metabolism.
Umezawa
K
K
Department of Biopharmaceutics, Tokyo College of Pharmacy.
Karino
A
A
Hayashi
M
M
Tahara
K
K
Kimura
A
A
Awazu
S
S
D000818:Animals; D001391:Azo Compounds / Q000493:pharmacokinetics*; D002250:Carbon Radioisotopes; D002478:Cells, Cultured; D002788:Cholesterol Esters / Q000493:pharmacokinetics*; D004655:Emulsions; D007728:Kupffer Cells / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D010477:Perfusion; D051381:Rats
D001391:Azo Compounds; D002250:Carbon Radioisotopes; D002788:Cholesterol Esters; D004655:Emulsions; C014409:cholesteryl oleate; C046548:fat red 7B