title: Pharmacokinetics of Naja sumatrana (equatorial spitting cobra) venom and its major toxins in experimentally envenomed rabbits.
abstract: BACKGROUND
  The optimization of snakebite management and the use of antivenom depend greatly on the knowledge of the venom's composition as well as its pharmacokinetics. To date, however, pharmacokinetic reports on cobra venoms and their toxins are still relatively limited. In the present study, we investigated the pharmacokinetics of Naja sumatrana (Equatorial spitting cobra) venom and its major toxins (phospholipase A2, neurotoxin and cardiotoxin), following intravenous and intramuscular administration into rabbits.
  
  
  RESULTS
  The serum antigen concentration-time profile of the N. sumatrana venom and its major toxins injected intravenously fitted a two-compartment model of pharmacokinetics. The systemic clearance (91.3 ml/h), terminal phase half-life (13.6 h) and systemic bioavailability (41.9%) of N. sumatrana venom injected intramuscularly were similar to those of N. sputatrix venom determined in an earlier study. The venom neurotoxin and cardiotoxin reached their peak concentrations within 30 min following intramuscular injection, relatively faster than the phospholipase A2 and whole venom (Tmax=2 h and 1 h, respectively). Rapid absorption of the neurotoxin and cardiotoxin from the injection site into systemic circulation indicates fast onsets of action of these principal toxins that are responsible for the early systemic manifestation of envenoming. The more prominent role of the neurotoxin in N. sumatrana systemic envenoming is further supported by its significantly higher intramuscular bioavailability (Fi.m.=81.5%) compared to that of the phospholipase A2 (Fi.m.=68.6%) or cardiotoxin (Fi.m.=45.6%). The incomplete absorption of the phospholipase A2 and cardiotoxin may infer the toxins' affinities for tissues at the injection site and their pathological roles in local tissue damages through synergistic interactions.
  
  
  CONCLUSIONS
  Our results suggest that the venom neurotoxin is absorbed very rapidly and has the highest bioavailability following intramuscular injection, supporting its role as the principal toxin in systemic envenoming.
authors.affiliation: CENAR and Department of Molecular Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Michelle Khai Khun
authors.initials: MK
authors.lastname: Yap
authors.affiliation: CENAR and Department of Molecular Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Nget Hong
authors.initials: NH
authors.lastname: Tan
authors.affiliation: Department of Pharmacology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Si Mui
authors.initials: SM
authors.lastname: Sim
authors.affiliation: CENAR and 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 Pharmacology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Choo Hock
authors.initials: CH
authors.lastname: Tan
mesh_terms: D000818:Animals; D001682:Biological Availability; D054715:Cardiotoxins / Q000493:pharmacokinetics*; D003039:Cobra Neurotoxin Proteins / Q000493:pharmacokinetics*; D004546:Elapid Venoms / Q000493:pharmacokinetics*; D017815:Elapidae; D006207:Half-Life; D007273:Injections, Intramuscular; D054467:Phospholipases A2 / Q000493:pharmacokinetics*; D011817:Rabbits
chemical_list: D054715:Cardiotoxins; D003039:Cobra Neurotoxin Proteins; D004546:Elapid Venoms; D054467:Phospholipases A2