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Intravenous Vipera berus Venom-Specific Fab Fragments and Intramuscular Vipera ammodytes Venom-Specific F(ab')2 Fragments in Vipera ammodytes-Envenomed Patients.
Toxins (Basel). 2021 04 14; 13(4)T

Abstract

Vipera ammodytes (V. ammodytes) is the most venomous European viper. The aim of this study was to compare the clinical efficacy and pharmacokinetic values of intravenous Vipera berus venom-specific (paraspecific) Fab fragments (ViperaTAb) and intramuscular V. ammodytes venom-specific F(ab')2 fragments (European viper venom antiserum, also called "Zagreb" antivenom) in V.ammodytes-envenomed patients. This was a prospective study of V.ammodytes-envenomed patients that were treated intravenously with ViperaTAb or intramuscularly with European viper venom antiserum that was feasible only due to the unique situation of an antivenom shortage. The highest venom concentration, survival, length of hospital stay and adverse reactions did not differ between the groups. Patients treated with intravenous Fab fragments were sicker, with significantly more rhabdomyolysis and neurotoxicity. The kinetics of Fab fragments after one or more intravenous applications matched better with the venom concentration in the early phase of envenomation compared to F(ab')2 fragments that were given intramuscularly only on admission. F(ab')2 fragments given intramuscularly had 25-fold longer apparent total body clearance and 14-fold longer elimination half-time compared to Fab fragments given intravenously (2 weeks vs. 24 h, respectively). In V.ammodytes-envenomed patients, the intramuscular use of specific F(ab')2 fragments resulted in a slow rise of antivenom serum concentration that demanded their early administration but without the need for additional doses for complete resolution of all clinical signs of envenomation. Intravenous use of paraspecific Fab fragments resulted in the immediate rise of antivenom serum concentration that enabled their use according to the clinical progress, but multiple doses might be needed for efficient therapy of thrombocytopenia due to venom recurrence, while the progression of rhabdomyolysis and neurotoxic effects of the venom could not be prevented.

Authors+Show Affiliations

Centre for Research and Knowledge Transfer in Biotechnology, University of Zagreb, Rockefellerova 10, 10000 Zagreb, Croatia. Center of Excellence for Virus Immunology and Vaccines, CERVirVac, Rockefellerova 10, 10000 Zagreb, Croatia.Clinical Department of Infectious Diseases, University Hospital of Split, Šoltanska 1, 21000 Split, Croatia. School of Medicine, University of Split, Šoltanska 2, 21000 Split, Croatia.Centre for Clinical Toxicology and Pharmacology, University Medical Centre Ljubljana, Zaloška cesta 7, 1000 Ljubljana, Slovenia.Centre for Clinical Toxicology and Pharmacology, University Medical Centre Ljubljana, Zaloška cesta 7, 1000 Ljubljana, Slovenia.Department of Molecular and Biomedical Sciences, Jožef Stefan Institute, Jamova 39, 1000 Ljubljana, Slovenia.Clinical Department of Infectious Diseases, University Hospital of Split, Šoltanska 1, 21000 Split, Croatia. School of Medicine, University of Split, Šoltanska 2, 21000 Split, Croatia.Centre for Research and Knowledge Transfer in Biotechnology, University of Zagreb, Rockefellerova 10, 10000 Zagreb, Croatia. Center of Excellence for Virus Immunology and Vaccines, CERVirVac, Rockefellerova 10, 10000 Zagreb, Croatia.Centre for Clinical Toxicology and Pharmacology, University Medical Centre Ljubljana, Zaloška cesta 7, 1000 Ljubljana, Slovenia. Centre for Clinical Physiology, Faculty of Medicine, University of Ljubljana, Zaloška cesta 4, 1000 Ljubljana, Slovenia.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

33919927

Citation

Kurtović, Tihana, et al. "Intravenous Vipera Berus Venom-Specific Fab Fragments and Intramuscular Vipera Ammodytes Venom-Specific F(ab')2 Fragments in Vipera ammodytes-Envenomed Patients." Toxins, vol. 13, no. 4, 2021.
Kurtović T, Karabuva S, Grenc D, et al. Intravenous Vipera berus Venom-Specific Fab Fragments and Intramuscular Vipera ammodytes Venom-Specific F(ab')2 Fragments in Vipera ammodytes-Envenomed Patients. Toxins (Basel). 2021;13(4).
Kurtović, T., Karabuva, S., Grenc, D., Dobaja Borak, M., Križaj, I., Lukšić, B., Halassy, B., & Brvar, M. (2021). Intravenous Vipera berus Venom-Specific Fab Fragments and Intramuscular Vipera ammodytes Venom-Specific F(ab')2 Fragments in Vipera ammodytes-Envenomed Patients. Toxins, 13(4). https://doi.org/10.3390/toxins13040279
Kurtović T, et al. Intravenous Vipera Berus Venom-Specific Fab Fragments and Intramuscular Vipera Ammodytes Venom-Specific F(ab')2 Fragments in Vipera ammodytes-Envenomed Patients. Toxins (Basel). 2021 04 14;13(4) PubMed PMID: 33919927.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Intravenous Vipera berus Venom-Specific Fab Fragments and Intramuscular Vipera ammodytes Venom-Specific F(ab')2 Fragments in Vipera ammodytes-Envenomed Patients. AU - Kurtović,Tihana, AU - Karabuva,Svjetlana, AU - Grenc,Damjan, AU - Dobaja Borak,Mojca, AU - Križaj,Igor, AU - Lukšić,Boris, AU - Halassy,Beata, AU - Brvar,Miran, Y1 - 2021/04/14/ PY - 2021/03/01/received PY - 2021/04/08/revised PY - 2021/04/12/accepted PY - 2021/4/30/entrez PY - 2021/5/1/pubmed PY - 2021/6/30/medline KW - European viper venom antiserum KW - F(ab’)2 fragments KW - Fab fragments KW - V. ammodytes KW - ViperaTAb KW - nose-horned viper KW - pharmacokinetics KW - “Zagreb” antivenom JF - Toxins JO - Toxins (Basel) VL - 13 IS - 4 N2 - Vipera ammodytes (V. ammodytes) is the most venomous European viper. The aim of this study was to compare the clinical efficacy and pharmacokinetic values of intravenous Vipera berus venom-specific (paraspecific) Fab fragments (ViperaTAb) and intramuscular V. ammodytes venom-specific F(ab')2 fragments (European viper venom antiserum, also called "Zagreb" antivenom) in V.ammodytes-envenomed patients. This was a prospective study of V.ammodytes-envenomed patients that were treated intravenously with ViperaTAb or intramuscularly with European viper venom antiserum that was feasible only due to the unique situation of an antivenom shortage. The highest venom concentration, survival, length of hospital stay and adverse reactions did not differ between the groups. Patients treated with intravenous Fab fragments were sicker, with significantly more rhabdomyolysis and neurotoxicity. The kinetics of Fab fragments after one or more intravenous applications matched better with the venom concentration in the early phase of envenomation compared to F(ab')2 fragments that were given intramuscularly only on admission. F(ab')2 fragments given intramuscularly had 25-fold longer apparent total body clearance and 14-fold longer elimination half-time compared to Fab fragments given intravenously (2 weeks vs. 24 h, respectively). In V.ammodytes-envenomed patients, the intramuscular use of specific F(ab')2 fragments resulted in a slow rise of antivenom serum concentration that demanded their early administration but without the need for additional doses for complete resolution of all clinical signs of envenomation. Intravenous use of paraspecific Fab fragments resulted in the immediate rise of antivenom serum concentration that enabled their use according to the clinical progress, but multiple doses might be needed for efficient therapy of thrombocytopenia due to venom recurrence, while the progression of rhabdomyolysis and neurotoxic effects of the venom could not be prevented. SN - 2072-6651 UR - https://www.unboundmedicine.com/medline/citation/33919927/Intravenous_Vipera_berus_Venom_Specific_Fab_Fragments_and_Intramuscular_Vipera_ammodytes_Venom_Specific_F_ab'_2_Fragments_in_Vipera_ammodytes_Envenomed_Patients_ L2 - https://www.mdpi.com/resolver?pii=toxins13040279 DB - PRIME DP - Unbound Medicine ER -