TY - JOUR T1 - Biodistribution and Pharmacokinetics of <sup>131</sup>I-Labeled LEX 032, A Recombinant Hybrid of Antichymotrypsin JF - Drug Metabolism and Disposition JO - Drug Metab Dispos SP - 631 LP - 636 VL - 25 IS - 5 AU - Howard Sands AU - Jirguhua Li AU - Ramana Duggaraju AU - Hemender R. Kolan AU - Michael Donegan AU - Gulnur A. Elove AU - Mathew L. Thakur Y1 - 1997/05/01 UR - http://dmd.aspetjournals.org/content/25/5/631.abstract N2 - Pharmacokinetic and biodistribution studies were conducted in rats on a novel serine protease inhibitor, LEX 032, that was radiolabeled with 131I by the Bolton-Hunter reagent. LEX 032, a genetically engineered recombinant human nonglycosylated serpin, has been shown to have antiinflammatory properties in a number of animal models of inflammation and reperfusion injury. When131I-LEX 032 was injected intravenously, a rapid whole body clearance of radioactivity was seen. Blood clearance followed a similar pattern. Forty-eight hours postinjection, 2.00 ± 0.65% of the administered dose remained in the body. Greater than 59% of the radioactivity was excreted in the urine within the first 24 hr. Little radioactivity was found in the feces. With the exception of the thyroid, no significant organ-related uptake was noted. Radioactivity in the liver peaked at 20 min postinjection, with 1.00 ± 0.13% administered dose/g and ∼10% administered dose in the whole liver. At 1 hr, uptake in the kidney (9.30 ± 1.52% administered dose/g) was the highest among all tissues, except for the thyroid. Gamma camera images were consistent with the biodistribution pattern. Pharmacokinetics and biodistribution were not affected by the dose of LEX 032 and were quite different from those of glycosylated wild type antichymotrypsin. These data indicate that LEX 032 exhibits the pharmacokinetics expected of a nonglycosylated 45 kDa protein. The American Society for Pharmacology and Experimental Therapeutics ER -