Premium
Quantitative evaluation of biliary elimination of gadoxetate, a magnetic resonance imaging contrast agent, via geometrical isomer‐specific transporting system in rats
Author(s) -
Ogawa Junji,
Yokota Azusa,
Araki Takuya,
Aomori Tohru,
Nakamura Tomonori,
Yamamoto Koujirou,
Koshiishi Ichiro
Publication year - 2014
Publication title -
biopharmaceutics and drug disposition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.419
H-Index - 58
eISSN - 1099-081X
pISSN - 0142-2782
DOI - 10.1002/bdd.1907
Subject(s) - magnetic resonance imaging , chemistry , in vivo , medicine , radiology , biology , microbiology and biotechnology
Gadoxetate, a magnetic resonance imaging contrast agent, is eliminated into bile. Gadoxetate geometrical isomers are chromatographically classified into two groups by differences between their ionic states (GIs‐I and GIs‐II; 65:35 w/w); however, the elimination mechanism of each isomer in vivo remains controversial. Thus, the contribution of carrier‐mediated transport systems on the biliary elimination of gadoxetate was examined. Gadoxetate was injected intravenously into rats, and the time courses of the plasma concentrations and biliary elimination of GIs‐I and GIs‐II were examined by high‐performance liquid chromatography techniques. The results showed that 34.7% of GIs‐I (GIs‐I(s); 22.6% of gadoxetate) was quickly eliminated into bile within 30 min after injection. The contents of the residual GIs‐I (GIs‐I(r)) and GIs‐II in plasma similarly decreased according to a first‐order elimination process ( t 1/2 = 23–27 min), and 64.0% of GIs‐I(r) and GIs‐II (49.6% of gadoxetate) was eliminated into the bile within 2 h after injection. There was no significant difference between the elimination half‐lives of GIs‐I(r) and GIs‐II in rats. In conclusion, the geometrical isomer with specific conformation corresponding to 22.6% of gadoxetate was eliminated into bile in rats via a carrier‐mediated transport system no later than 30 min after intravenous injection. Copyright © 2014 John Wiley & Sons, Ltd.