title: Pharmacokinetics of the Sri Lankan hump-nosed pit viper (Hypnale hypnale) venom following intravenous and intramuscular injections of the venom into rabbits.
abstract: The knowledge of venom pharmacokinetics is essential to improve the understanding of envenomation pathophysiology. Using a double-sandwich ELISA, this study investigated the pharmacokinetics of the venom of hump-nosed pit viper (Hypnale hypnale) following intravenous and intramuscular injections into rabbits. The pharmacokinetics of the venom injected intravenously fitted a three-compartment model. There is a rapid (t1/2π = 0.4 h) and a slow (t1/2α = 0.8 h) distribution phase, followed by a long elimination phase (t1/2β = 19.3 h) with a systemic clearance of 6.8 mL h(-1) kg(-1), consistent with the prolonged abnormal hemostasis reported in H. hypnale envenomation. On intramuscular route, multiple peak concentrations observed in the beginning implied a more complex venom absorption and/or distribution pattern. The terminal half-life, volume of distribution by area and systemic clearance of the venom injected intramuscularly were nevertheless not significantly different (p > 0.05) from that of the venom injected intravenously. The intramuscular bioavailability was exceptionally low (Fi.m. = 4%), accountable for the highly varied median lethal doses between intravenous and intramuscular envenomations in animals. The findings indicate that the intramuscular route of administration does not significantly alter the pharmacokinetics of H. hypnale venom although it significantly reduces the systemic bioavailability of the venom.
authors.affiliation: Department of Pharmacology, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia. Electronic address: tanchoohock@gmail.com.
authors.forename: Choo Hock
authors.initials: CH
authors.lastname: Tan
authors.affiliation: Department of Pharmacology, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia.
authors.forename: Si Mui
authors.initials: SM
authors.lastname: Sim
authors.affiliation: Department of Clinical Medicine, Faculty of Medicine, University of Colombo, Sri Lanka.
authors.forename: Christeine Ariaranee
authors.initials: CA
authors.lastname: Gnanathasan
authors.affiliation: Department of Molecular Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Shin Yee
authors.initials: SY
authors.lastname: Fung
authors.affiliation: Department of Molecular Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Nget Hong
authors.initials: NH
authors.lastname: Tan
mesh_terms: D000818:Animals; D000997:Antivenins / Q000097:blood; D019540:Area Under Curve; D004797:Enzyme-Linked Immunosorbent Assay; D006735:Horseradish Peroxidase / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D007273:Injections, Intramuscular; D007275:Injections, Intravenous; D007928:Lethal Dose 50; D011817:Rabbits; D012909:Snake Bites / Q000473:pathology* / Q000628:therapy; D013188:Sri Lanka; D014757:Viper Venoms / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D017819:Viperidae
chemical_list: D000997:Antivenins; D007074:Immunoglobulin G; D014757:Viper Venoms; D006735:Horseradish Peroxidase
keywords: ELISA; Hump-nosed pit viper; Hypnale hypnale; Intramuscular bioavailability; Snake envenomation; Venom pharmacokinetics