In vivo stability and excretion of gadodiamide (GdDTPA-BMA), a hydrophilic gadolinium complex used as a contrast enhancing agent for magnetic resonance imaging.
The stability and excretion of [14C]-gadodiamide (GdDTPA-BMA) was studied in male rats after i.v. injection of 0.3 mmol/kg [14C]-GdDTPA-BMA (Gd-diethylenetriaminepentaacetic-acid-bis-methylamide) formulated as gadodiamide injection (OMNISCAN, Nycomed Imaging AS, Oslo, Norway). Samples of blood and urine obtained within 60 min and 6 h postdosing, respectively, were analyzed for radiolabeled compounds. Analysis of GdDTPA-BMA in high and low molecular weight fractions of serum indicated no protein binding. HPLC analyses of urine samples obtained 0-2 h, 2-4 h and 4-6 h after injection revealed no detectable amounts of biotransformation products of GdDTPA-BMA. Serum samples obtained 30 min and 60 min after injection contained 9-13 microM of an unidentified compound which had a retention time different from all conceivable metabolites of gadodiamide. A similar concentration of this unknown compound was found in spiked predose serum samples. The total amount of the unknown compound in serum was less than 1% of the injected dose of [14C]-gadodiamide injection. It is concluded that gadodiamide, when administered i.v. as gadodiamide injection at a dosage of 0.3 mmol/kg, is stable in vivo and that the very major part of the dose (> 99%) is excreted in urine as an unchanged complex.
Normann
P T
PT
Research and Development, Nycomed Imaging AS, Oslo, Norway.
Hals
P A
PA
D000818:Animals; D001711:Biotransformation; D002851:Chromatography, High Pressure Liquid; D003287:Contrast Media / Q000493:pharmacokinetics*; D004355:Drug Stability; D019786:Gadolinium DTPA; D007275:Injections, Intravenous; D008297:Male; D009942:Organometallic Compounds / Q000493:pharmacokinetics*; D004369:Pentetic Acid / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar
D003287:Contrast Media; D009942:Organometallic Compounds; D004369:Pentetic Acid; C064925:gadodiamide; D019786:Gadolinium DTPA