The disposition of suramin in the isolated perfused rat liver

We have investigated the disposition of suramin in the isolated perfused rat liver preparation (IPRL) after the administration of suramin (18 mg, 8 muCi). At 30 min post drug administration, almost 100% of the [14C]radioactivity and unchanged suramin were located in the perfusate plasma. During the course of the study, the elimination of suramin from the IPRL was barely perceptible. The AUC0-5 hr of suramin (730.6 +/- 86.2 micrograms hr/ml) corresponded to that of [14C] radioactivity (815.1 +/- 105.5 micrograms ml/hr) at 5 hr, indicating a lack of perfusate suramin metabolites. At 5 hr only a small proportion of [14C] radioactivity was recovered from the livers (2.5 +/- 1.1%). Subsequent HPLC analysis of the liver tissue indicated this to be unchanged suramin. Sub-cellular fractionation of the homogenised livers revealed suramin to be distributed in the liposomal rich tissue fractions (10,000 g pellet, 1.6 +/- 0.8%; 105,000 g supernatant, 1.1 +/- 0.35%). Biliary excretion of [14C] radioactivity was low (2.1 +/- 0.7%), however, none could be accounted for as unchanged suramin. Previously undetected metabolites of suramin may have accounted for the unidentified biliary radioactivity.