title: Vipera ammodytes bites treated with antivenom ViperaTAb: a case series with pharmacokinetic evaluation.
abstract: BACKGROUND
  In clinical practice it is difficult to differentiate between V. berus and V. ammodytes venomous bites. In the past this was not a concern, but due to the current shortage in Viperfav™ and European viper venom antiserum availability, V. a. ammodytes venomous bites have recently been treated with ViperaTAb®, which is a pharmaceutical formulation containing a monospecific ovine Fab fragments against the venom of V. berus.
  
  
  OBJECTIVE
  To evaluate ViperaTAb®in V. a. ammodytes envenomations.
  
  
  METHODS
  This is a prospective case series of three consecutive patients envenomed by V. a. ammodytes snakebite treated with ViperaTAb®. V. ammodytes venom, neurotoxic ammodytoxins, and Fab fragment levels were determined in serum samples and a pharmacokinetic analysis of the antivenom Fab fragments was carried out.
  
  
  RESULTS
  Three patients bitten by V. a. ammodytes with extensive local swelling, neurological symptoms and recurrent thrombocytopenia were treated with ViperaTAb®. V. ammodytes venom was detected in serum of all three patients. Ammodytoxins were detected in the serum of only the most severely envenomed patient who developed neurological symptoms. In the presented moderate cases, a dose of 8 mL of ViperaTAb®reduced swelling and improved systemic effects, such as thrombocytopenia. However, this dose of ViperaTAb®was not effective in the most severely envenomed patient with the highest serum values of V. ammodytes venom. In this case ViperaTAb®did not stop local swelling and it had no effect on neurological signs. ViperaTAb®'s systemic clearance, distribution and elimination half-lives were 4.3-13.4 mL/h/kg, 1.2-3.2 h and 14.1-55.4 h, respectively.
  
  
  CONCLUSIONS
  In patients envenomed by V. a. ammodytes venom, ViperaTAb®reduces moderate swelling and temporarily improves systemic effects, except neurological symptoms. ViperaTAb®application induces a decrement of V. ammodytes venom level in the blood, but did not affect serum concentration of neurotoxic ammodytoxins in the one patient with measurable concentrations.
authors.affiliation: a Centre for Clinical Toxicology and Pharmacology, University Medical Centre Ljubljana , Ljubljana , Slovenia.|b Faculty of Medicine , Institute of Pathophysiology, University of Ljubljana , Ljubljana , Slovenia.
authors.forename: Miran
authors.initials: M
authors.lastname: Brvar
authors.affiliation: c Centre for Research and Knowledge Transfer in Biotechnology, University of Zagreb , Zagreb , Croatia.
authors.forename: Tihana
authors.initials: T
authors.lastname: Kurtović
authors.affiliation: a Centre for Clinical Toxicology and Pharmacology, University Medical Centre Ljubljana , Ljubljana , Slovenia.
authors.forename: Damjan
authors.initials: D
authors.lastname: Grenc
authors.affiliation: c Centre for Research and Knowledge Transfer in Biotechnology, University of Zagreb , Zagreb , Croatia.
authors.forename: Maja
authors.initials: M
authors.lastname: Lang Balija
authors.affiliation: d Department of Molecular and Biomedical Sciences , Jožef Stefan Institute , Ljubljana , Slovenia.|e Faculty of Chemistry and Chemical Technology , University of Ljubljana , Ljubljana , Slovenia.
authors.forename: Igor
authors.initials: I
authors.lastname: Križaj
authors.affiliation: c Centre for Research and Knowledge Transfer in Biotechnology, University of Zagreb , Zagreb , Croatia.
authors.forename: Beata
authors.initials: B
authors.lastname: Halassy
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D000932:Antiemetics / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D000997:Antivenins / Q000097:blood / Q000627:therapeutic use*; D004636:Emergency Service, Hospital; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000097:blood / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012909:Snake Bites / Q000097:blood / Q000188:drug therapy*; D013847:Thiethylperazine / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D014757:Viper Venoms / Q000633:toxicity*; D017819:Viperidae
chemical_list: D000932:Antiemetics; D000997:Antivenins; D007140:Immunoglobulin Fab Fragments; D014757:Viper Venoms; D013847:Thiethylperazine
keywords: Fab fragments; V. a. ammodytes; ViperaTAb; nose-horned viper; pharmacokinetics