Abstract
After intravenous (iv) injection of125I-labeled poly(ethylene glycol) (PEG) with different molecular weights to mice, the radioactivity of the organs was measured to pharmacokinetically analyze the body distribution of PEG according to a two-compartment model. High molecular weight PEGs were retained in the blood circulation for a longer period than low molecular weight PEGs. The terminal half-life of PEG in the circulation extended from 18 min to 1 day as the PEG molecular weight increased from 6000 to 190 000. PEG tended to accumulate in the tissues/organs such as muscle, skin, bone, and the liver to a higher extent than the other organs, irrespective of the molecular weight. The time dependence of tissue accumulation was based on the vascular permeability. The results of pharmacokinetic analysis suggested that small PEG tended to freely translocate from the circulation to extravascular tissues and to return to the blood circulation again by diffusion, whereas large PEG translocated more slowly to extravascular tissues. Urinary clearance decreased with increasing PEG molecular weight, similar to the tissue clearance, whereas liver clearance increased with the increasing PEG molecular weight, after passing a minimum around the molecular weight of 50 000. PEG uptake by Kupffer cells was enhanced as the molecular weight became >50 000.
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