LYMPHATIC ROUTE OF TRANSPORT AND PHARMACOKINETICS OF MICRURUS FULVIUS (CORAL SNAKE) VENOM IN SHEEP

Abstract

The contribution of the lymphatic systemto the absorption and systemic bioavailabilityof Micrurus fulvius venom after subcutaneous(SC) administration was assessed using acentral lymph-cannulated sheep model.Micrurus fulvius venom was administeredeither by intravenous bolus (IV) orsubcutaneous injection (SC) in 12 sheep withand without thoracic duct cannulation anddrainage. Venom concentration in serum andlymph was determined by a sandwich enzymelinkedimmunosorbent assay (ELISA) insamples collected over a 6-hour period and intissues harvested at the end of the experiment.Pharmacokinetic parameters were determinedby a non-compartmental analysis. In thelymphatic cannulated group, over the 6 hoursafter the venom was administered, 69% ofadministered dose was accounted for in blood(45%) and lymph (25%). Negligible levels ofvenom were detected in organs and urineimplying that the steady state observed afterSC administration is maintained by a slowabsorption process. Comparison of kinetics ofthe thoracic duct cannulated and noncannulatedgroups showed that lymphaticabsorption contributed in an important wayto maintenance of this steady state. Theseresults show that the limiting process in thepharmacokinetics of Micrurus fulvius venomfollowing SC administration is absorption,and that the lymphatic system plays a key rolein this process.