Magnetic resonance imaging of the hepatobiliary system: intestinal absorption studies of manganese mesoporphyrin.
OBJECTIVE
We studied the intestinal absorption of manganese mesoporphyrin (Mn-mesoporphyrin), a potential oral hepatobiliary contrast agent.


METHODS
Mn-mesoporphyrin was complexed with monoolein and taurocholate (mixed micelles). Portal venous delivery and biliary excretion were measured after intestinal administration in rats and rabbits, and the mechanism of intestinal transport was studied in a combined lymph-bile fistula model in rats. T1-weighted magnetic resonance (MR) images of the liver were obtained in rats and domestic pigs before and after gastric administration of Mn-mesoporphyrin in mixed micelles.


RESULTS
A 2.2-fold increase of portal venous Mn concentration was found 90 min after intestinal administration of the complex. None was found in the lymph collected from the thoracic duct, indicating a transcellular transport mechanism through the intestinal mucosa with portal venous delivery. Mn-mesoporphyrin levels in bile peaked between 240 and 270 min after administration (200-fold increase). The greatest liver enhancement (20-90%) was measured 360 min after administration.


CONCLUSIONS
The feasibility of intestinal delivery of Mn-mesoporphyrin, a lipophilic hepatobiliary contrast agent was demonstrated.
Schmiedl
U P
UP
Department of Radiology, University of Washington School of Medicine, Seattle, USA.
Nelson
J A
JA
Teng
L
L
Starr
F
F
Malek
R
R
Ho
R J
RJ
D000818:Animals; D003287:Contrast Media / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005682:Gadolinium / Q000493:pharmacokinetics; D005989:Glycerides / Q000008:administration & dosage; D007408:Intestinal Absorption / Q000502:physiology*; D008099:Liver / Q000033:anatomy & histology*; D008279:Magnetic Resonance Imaging; D008345:Manganese / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008652:Mesoporphyrins / Q000008:administration & dosage / Q000493:pharmacokinetics*; D011169:Portal Vein / Q000033:anatomy & histology*; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar; D013552:Swine; D013656:Taurocholic Acid / Q000008:administration & dosage
D003287:Contrast Media; D005989:Glycerides; D008652:Mesoporphyrins; C067090:manganese mesoporphyrin; D008345:Manganese; D013656:Taurocholic Acid; D005682:Gadolinium; C005953:monoolein