DISTRIBUTION AND ELIMINATION OF BREVETOXIN PBTX-3 IN RATS

After i.v. administration, [3H]PbTx-3 was rapidly cleared from the blood; less than 10% remained after 1 min. Within 30 min, radiolabel distributed to skeletal muscle (69.5%), liver (18.0%), and intestinal tract (8.0%). Over 24 hr, radiolabel decreased in muscle, remained constant in liver, and increased in the intestinal tract and feces. Elimination occurred via feces (75.1%) and urine (14.4%), with 9.0% remaining in the carcass after 6 days. This distribution and elimination profile suggested that the liver was the major organ of metabolism and that biliary excretion was an important route of elimination. Thin-layer chromatography confirmed the presence of brevetoxin metabolites in fecal extracts. Skeletal muscle does not appear to be a site of metabolism, but a storage compartment, from which toxin is slowly released prior to clearance by the liver. These studies are the first demonstration of in vivo brevetoxin metabolism in mammals. © 1990.