title: Lymphatic route of transport and pharmacokinetics of Micrurus fulvius (coral snake) venom in sheep.
abstract: The contribution of the lymphatic system to the absorption and systemic bioavailability of Micrurus fulvius venom after subcutaneous (SC) administration was assessed using a central lymph-cannulated sheep model. Micrurus fulvius venom was administered either by intravenous bolus (IV) or subcutaneous injection (SC) in 12 sheep with and without thoracic duct cannulation and drainage. Venom concentration in serum and lymph was determined by a sandwich enzyme-linked immunosorbent assay (ELISA) in samples collected over a 6-hour period and in tissues harvested at the end of the experiment. Pharmacokinetic parameters were determined by a non-compartmental analysis. In the lymphatic cannulated group, over the 6 hours after the venom was administered, 69% of administered dose was accounted for in blood (45%) and lymph (25%). Negligible levels of venom were detected in organs and urine implying that the steady state observed after SC administration is maintained by a slow absorption process. Comparison of kinetics of the thoracic duct cannulated and non-cannulated groups showed that lymphatic absorption contributed in an important way to maintenance of this steady state. These results show that the limiting process in the pharmacokinetics of Micrurus fulvius venom following SC administration is absorption, and that the lymphatic system plays a key role in this process.
authors.affiliation: Instituto de Biotecnología, Universidad Nacional Autónoma de México, Cuernavaca, México.
authors.forename: D
authors.initials: D
authors.lastname: Paniagua
authors.forename: L
authors.initials: L
authors.lastname: Jiménez
authors.forename: C
authors.initials: C
authors.lastname: Romero
authors.forename: I
authors.initials: I
authors.lastname: Vergara
authors.forename: A
authors.initials: A
authors.lastname: Calderón
authors.forename: M
authors.initials: M
authors.lastname: Benard
authors.forename: M J
authors.initials: MJ
authors.lastname: Bernas
authors.forename: H
authors.initials: H
authors.lastname: Rilo
authors.forename: A
authors.initials: A
authors.lastname: de Roodt
authors.forename: G
authors.initials: G
authors.lastname: D' Suze
authors.forename: M H
authors.initials: MH
authors.lastname: Witte
authors.forename: L
authors.initials: L
authors.lastname: Boyer
authors.forename: A
authors.initials: A
authors.lastname: Alagón
mesh_terms: D000818:Animals; D019540:Area Under Curve; D001682:Biological Availability; D001692:Biological Transport; D004546:Elapid Venoms / Q000008:administration & dosage / Q000493:pharmacokinetics*; D017815:Elapidae; D005260:Female; D006207:Half-Life; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D008208:Lymphatic System / Q000378:metabolism*; D008297:Male; D012756:Sheep; D034561:Sheep, Domestic / Q000378:metabolism*; D014018:Tissue Distribution
chemical_list: D004546:Elapid Venoms