Alteration of the pharmacokinetics of small proteins by iodination

Biopharmaceutics & Drug Disposition
R J BauerA H Kung

Abstract

The pharmacokinetics of several proteins were investigated using two different assays. A 23 kDa recombinant protein fragment of bactericidal/permeability-increasing protein (rBPI23) was radiolabeled with 125I using Iodo-beads and administered rats. Plasma samples were collected and assayed for 125I-rBPI23 by radioactivity. In a separate experiment, rBPI23 was administered to rats and plasma samples were assayed for rBPI23 by ELISA. The clearance determined from plasma concentrations of 125I-rBPI23 measured by radioactivity was about 2.5-fold lower than that of rBPI23 determined by ELISA. In addition, the steady state volumes of distribution and mean residence times of 125I-rBPI23 measured by radioactivity were four-fold and 10-fold greater, respectively, compared to those measured by the ELISA method. By studying several proteins with a range of molecular weights, we found that the pharmacokinetics of proteins below about 60 kDa were different when assayed by radioactivity or ELISA, but those of proteins with molecular weights of at least 80 kDA revealed only minor differences. To determine which assay method yielded the correct plasma pharmacokinetic profile, rBPI23 was metabolically labeled with 35S-methionine and administere...Continue Reading

Citations

Sep 19, 2007·Journal of Industrial Microbiology & Biotechnology·Okom Nkili F C Ofodile
Jun 17, 2003·Journal of Toxicology. Clinical Toxicology·David G Lalloo, R David G Theakston
Jan 6, 1999·Journal of Pharmaceutical Sciences·G HongJ M Scherrmann
Apr 27, 2001·Pain·S BinghamA A Parsons
Mar 1, 1997·Journal of Pharmaceutical Sciences·B S KuoD S Wright

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