TOXICOKINETICS OF TRITIATED DIHYDROMICROCYSTIN-LR IN SWINE

The toxicokinetics of tritiated dihydromicrocystin-LR ([H-3]2H-MCLR) w ere studied in anesthetized, specific-pathogen-free pigs. Pigs were do sed with radiolabeled plus non-labeled 2H-MCLR at 25 or 75 mu g/kg i.v ., or via an isolated ileal loop at 75 mu g/kg. The i.v. doses were ra pidly removed from the blood. At either i.v. dose, more than half the radiolabel from [H-3]2H-MCLR present in the blood at 1 min postdosing was cleared by 6 min. The blood clearance at the 75 mu g/kg dose was s lower than at the 25 mu g/kg dose. Accordingly, at the high dose, the concentrations of the toxin in blood were disproportionately higher fr om 10 min after dosing until the study ended 4 hr later. The decreased clearance is presumably due to decreased elimination from the blood a s a consequence of the hepatic injury that was observed histologically . Following administration of [H-3]2H-MCLR at 75 mu g/kg via the ileum , the maximal toxin concentration in blood was achieved at 90 min afte r dosing. At that time the [H-3]2H-MCLR concentration in portal venous blood was 3.6 times higher than in peripheral venous blood. Although bile production varied, following i.v. dosing radioactivity was detect ed in bile as early as 12 min postdosing in one animal. This study dem onstrated that [H-3]2H-MCLR is rapidly removed from the blood of anest hetized swine and that excretion of the radiolabel into bile may begin within 30 min of dosing. (C) 1997 Elsevier Science Ltd.