TY - JOUR T1 - Pharmacokinetics and Hepatic Disposition of Bis[1-(ethoxycarbonyl)propyl]5-acetylamino-2,4,6-triiodoisophthalate in Rats and Isolated Perfused Rat Livers JF - Drug Metabolism and Disposition JO - Drug Metab Dispos SP - 731 LP - 736 VL - 28 IS - 7 AU - Yong Liu AU - Edward R. Bacon AU - Kelly Ballinger AU - Christopher D. V. Black AU - Kathleen Illig AU - Gregory L. McIntire AU - Ping Ping Wang AU - Nancy O'Neil AU - Lew Kinter AU - Vinay C. Desai Y1 - 2000/07/01 UR - http://dmd.aspetjournals.org/content/28/7/731.abstract N2 - Bis[1-(Ethoxycarbonyl)propyl]5-acetylamino-2,4,6-triiodoisophthalate (NC 68183) was designed as a new computed tomography imaging agent. The purpose of this study was to determine the pharmacokinetics and metabolism of NC 68183 in conscious rats and in the isolated perfused rat liver. Animals were i.v. dosed at 69 and 690 mg of iodine/kg. Blood samples were collected at 5, 15, 30, and 60 min, and 7 days after dosing. Tissue samples (liver, kidney, and spleen) were taken at 60 min and 7 days after dosing. NC 68183 was cleared from blood in first order kinetics following an i.v. administration of 69 mg I/kg. The volume of distribution (Vss) at steady state and elimination half-life (t1/2) were estimated as 24 ml and 11 min. The clearance of NC 68183 from blood was changed to zero-order kinetics following administration of 690 mg/kg, and its elimination rate was 16 μg I/ml·min. The liver and spleen were the only tissues to have the nanoparticle residue at day 7 following administration. NC 68183 (75 mg of agent, 35 mg of I) was injected into the isolated perfused rat liver system. Bile flow increased from 1.0 to 1.3 μl/min/g liver following administration. The biliary excretion rate maximum was estimated as 11 μg/min/g liver. The metabolite was identified using liquid chromatography/mass spectrometry as a monocarboxylic acid product, which exclusively excreted into the bile in a soluble iodinated metabolite. Pharmacokinetics data suggested that NC 68183 primarily resides in the blood pool following an i.v. administration with a plasma half-life appropriate for blood pool imaging. The American Society for Pharmacology and Experimental Therapeutics ER -