BODY DISTRIBUTION OF INTRAVENOUSLY ADMINISTERED GELATIN WITH DIFFERENT MOLECULAR-WEIGHTS

Radiolabelled gelatin with average molecular weights (M(w)) of 2700, 9 700, 56 000 and 99 000 was intravenously administered to mice to study the change of body distribution with time. The half-life period of ge latin in the blood circulation ranged from 7.8 min for M(w) of 2700 to 315 min for M(w) of 99000. When compared at a similar M(w), the half- life period of gelatin was always shorter than that of poly(ethylene g lycol) and poly(vinyl alcohol) which were also water-soluble polymers but not ionically charged. The gelatin molecules intravenously adminis tered were hardly accumulated in heart, lungs and spleen, but mostly i n carcass and finally excreted from kidneys. Staying of low-M(w) gelat in in liver was not significant although the amount accumulated tended to increase with M(w). The time course of gelatin accumulation in the carcass exhibited a peak within 20 min after intravenous administrati on except for gelatin with M(w) of 99000 which was much slowly accumul ated to the carcass during the initial 3 h after injection. The excret ion rate of gelatin to urine increased with M(w), but 60% of gelatin w as excreted from the body 400 min after intravenous injection even for the highest M(w). Moreover, pharmacokinetic analysis demonstrated tha t the tissue clearance of gelatin was higher than that of other polyme rs although the excretion clearance was similar, irrespective of the p olymer type and M(w). This indicates that gelatin tends to be distribu ted more dominantly from the plasma to tissues than other polymers, le ading to a shorter half-life period in the circulation.