engleski

Intravenous anti-V. berus Fab fragments and intramuscular anti-V. ammodytes F(ab')2 fragments in V. ammodytes-envenomed patients

Before 2015, snakebites caused by Vipera ammodytes were successfully treated with intravenous Viperfav (France), a formulation containing polyvalent equine F(ab')2 fragments against the venoms of V. aspis, V. berus and V. ammodytes, or intramuscular "Zagreb" antivenom (Croatia) composed of monospecific equine F(ab')2 fragments against V. ammodytes venom. During the period of their shortage, in Slovenia V. ammodytes bites were managed with ViperaTAb (UK), a formulation containing monospecific ovine Fab fragments against the venom of V. berus, whose eligibility for use in the clinical setting hasn't been previously assessed despite its different specificity and type of bioactive compound. "Zagreb" antivenom was continuously used in Croatia. Newly established treatment approach opened up the possibility for a comparative study of V. ammodytes-envenomed patients that were treated intravenously with ViperaTAb or intramuscularly with "Zagreb" antivenom. The aim was to gain insight into pharmacokinetic profiles of two antivenoms and to resolve their influence on venom level decrement as well on resolution of envenomation pathology, providing findings that might serve as useful guidance to clinicians. The kinetics of Fab fragments after one or more i.v. applications was characterized by immediate rise in systemic circulation and matched better with the venom concentration in the early envenomation phase, enabling their use according to the clinical progress. Multiple doses were needed for efficient therapy of edema and thrombocytopenia due to venom recurrence, while the progression of rhabdomyolysis and neurotoxic effects could not be prevented. The intramuscular use of F(ab')2 fragments resulted in slower increase of their level in the bloodstream. They had 25- and 14-fold longer clearance and elimination half-time, respectively, compared to Fab fragments given i.v. Such pharmacokinetic behavior demands for early administration but without need for additional doses.

V. ammodytes ; ViperaTAb ; “Zagreb” antivenom ; Fab fragments ; F(ab’)2 fragments ; pharmacokinetics

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