title: Quantitative evaluation of biliary elimination of gadoxetate, a magnetic resonance imaging contrast agent, via geometrical isomer-specific transporting system in rats.
abstract: 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 (t1/2=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.
authors.affiliation: Department of Pharmacy, Gunma University Hospital, Gunma, Japan.
authors.forename: Junji
authors.initials: J
authors.lastname: Ogawa
authors.forename: Azusa
authors.initials: A
authors.lastname: Yokota
authors.forename: Takuya
authors.initials: T
authors.lastname: Araki
authors.forename: Tohru
authors.initials: T
authors.lastname: Aomori
authors.forename: Tomonori
authors.initials: T
authors.lastname: Nakamura
authors.forename: Koujirou
authors.initials: K
authors.lastname: Yamamoto
authors.forename: Ichiro
authors.initials: I
authors.lastname: Koshiishi
mesh_terms: D000818:Animals; D001646:Bile / Q000378:metabolism; D001692:Biological Transport; D002851:Chromatography, High Pressure Liquid; D003287:Contrast Media / Q000737:chemistry* / Q000493:pharmacokinetics*; D019786:Gadolinium DTPA / Q000097:blood / Q000737:chemistry* / Q000493:pharmacokinetics*; D006207:Half-Life; D065669:Hepatobiliary Elimination; D007536:Isomerism; D008279:Magnetic Resonance Imaging; D008297:Male; D008968:Molecular Conformation; D017208:Rats, Wistar
chemical_list: D003287:Contrast Media; C073590:gadolinium ethoxybenzyl DTPA; D019786:Gadolinium DTPA
keywords: HPLC; biliary excretion; conformation; geometrical isomers; organic anion transporter polypeptide