Synthesis characterization and in vivo disposition of iodinatable polyethylene glycol derivatives differences in vivo as a function of chain length

A series of iodinatable water soluble polyethylene glycol (PEG) derivatives were prepared for use as model hydrophilic drugs. Polyethylene glycol diamine 6000 was coupled to methyl p-hydroxybenzimidate, and PEG 1900- and PEG 5000-monomethyl ethers were coupled to tyramine and histamine. The derivatives underwent facile iodination with the chloramine-T reaction and were stable under a wide range of conditions. The larger derivatives showed rapid renal clearance, but the 1900 MW compounds underwent significant clearance via the bile.