Association with oleic acid vesicles enhances manganese III mesoporphyrin absorption and biliary elimination in rats.
OBJECTIVE
To determine whether the association of manganese III mesoporphyrin (MnMeso), an oral MR contrast agent, to oleic acid (OA) vesicles will improve absorption and delivery of MnMeso to the liver.


METHODS
MnMeso or MnMeso-OA vesicle suspension was intraduodenally administered to rats and the time course of MnMeso concentration in plasma, bile, and intestinal solution was determined. Tissue concentrations of MnMeso in the liver were also determined.


RESULTS
Association of MnMeso to OA reduced the time it took to reach one-half absorption maximum, TC50, and enhanced the rate and the extent of biliary elimination of this contrast agent. In addition, the results obtained from dose-titration studies indicate that MnMeso-OA vesicle complex may enhance MnMeso accumulation in the liver, observed as a lower dose required to reach equivalent tissue concentration. Taken together, complexion to OA vesicles may provide rapid absorption, enhanced liver accumulation, and efficient elimination of MnMeso.


CONCLUSIONS
Association with OA vesicles may enhance the rate of MnMeso absorption and biliary excretion while promoting the extent of liver accumulation of MnMeso in rats. This strategy may provide a means to provide safe and effective use of MnMeso as an MR contrast medium.
Liu
T
T
Department of Pharmaceutics, University of Washington, Seattle 98195-7610, USA.
Bui
T
T
Schmiedl
U P
UP
Ho
R J
RJ
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D003287:Contrast Media / Q000737:chemistry* / Q000493:pharmacokinetics*; D004337:Drug Carriers; D006863:Hydrogen-Ion Concentration; D007408:Intestinal Absorption; D008099:Liver / Q000378:metabolism*; D008279:Magnetic Resonance Imaging; D008297:Male; D008345:Manganese / Q000737:chemistry* / Q000493:pharmacokinetics*; D008652:Mesoporphyrins / Q000737:chemistry* / Q000493:pharmacokinetics*; D009829:Oleic Acids / Q000737:chemistry*; D051381:Rats; D017208:Rats, Wistar
D003287:Contrast Media; D004337:Drug Carriers; D008652:Mesoporphyrins; D009829:Oleic Acids; C067090:manganese mesoporphyrin; D008345:Manganese