Intravenous <i>Vipera berus</i> Venom-Specific Fab Fragments and Intramuscular <i>Vipera ammodytes</i> Venom-Specific F(ab’)<sub>2</sub> Fragments in <i>Vipera ammodytes</i>-Envenomed Patients
<i>Vipera ammodytes</i> (<i>V. ammodytes</i>) is the most venomous European viper. The aim of this study was to compare the clinical efficacy and pharmacokinetic values of intravenous <i>Vipera berus</i> venom-specific (paraspecific) Fab fragments (ViperaTAb) and...
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MDPI AG
2021-04-01
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| Series: | Toxins |
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| Online Access: | https://www.mdpi.com/2072-6651/13/4/279 |
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| author | Tihana Kurtović Svjetlana Karabuva Damjan Grenc Mojca Dobaja Borak Igor Križaj Boris Lukšić Beata Halassy Miran Brvar |
| author_facet | Tihana Kurtović Svjetlana Karabuva Damjan Grenc Mojca Dobaja Borak Igor Križaj Boris Lukšić Beata Halassy Miran Brvar |
| author_sort | Tihana Kurtović |
| collection | DOAJ |
| description | <i>Vipera ammodytes</i> (<i>V. ammodytes</i>) is the most venomous European viper. The aim of this study was to compare the clinical efficacy and pharmacokinetic values of intravenous <i>Vipera berus</i> venom-specific (paraspecific) Fab fragments (ViperaTAb) and intramuscular <i>V. ammodytes</i> venom-specific F(ab’)<sub>2</sub> fragments (European viper venom antiserum, also called “Zagreb” antivenom) in <i>V.</i><i>ammodytes</i>-envenomed patients. This was a prospective study of <i>V.</i><i>ammodytes</i>-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’)<sub>2</sub> fragments that were given intramuscularly only on admission. F(ab’)<sub>2</sub> 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 <i>V.</i><i>ammodytes</i>-envenomed patients, the intramuscular use of specific F(ab’)<sub>2</sub> 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. |
| first_indexed | 2024-03-10T12:19:34Z |
| format | Article |
| id | doaj.art-99be788e5ad04cee8716e66828b08092 |
| institution | Directory Open Access Journal |
| issn | 2072-6651 |
| language | English |
| last_indexed | 2024-03-10T12:19:34Z |
| publishDate | 2021-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Toxins |
| spelling | doaj.art-99be788e5ad04cee8716e66828b080922023-11-21T15:35:06ZengMDPI AGToxins2072-66512021-04-0113427910.3390/toxins13040279Intravenous <i>Vipera berus</i> Venom-Specific Fab Fragments and Intramuscular <i>Vipera ammodytes</i> Venom-Specific F(ab’)<sub>2</sub> Fragments in <i>Vipera ammodytes</i>-Envenomed PatientsTihana Kurtović0Svjetlana Karabuva1Damjan Grenc2Mojca Dobaja Borak3Igor Križaj4Boris Lukšić5Beata Halassy6Miran Brvar7Centre for Research and Knowledge Transfer in Biotechnology, University of Zagreb, Rockefellerova 10, 10000 Zagreb, CroatiaClinical Department of Infectious Diseases, University Hospital of Split, Šoltanska 1, 21000 Split, CroatiaCentre for Clinical Toxicology and Pharmacology, University Medical Centre Ljubljana, Zaloška cesta 7, 1000 Ljubljana, SloveniaCentre for Clinical Toxicology and Pharmacology, University Medical Centre Ljubljana, Zaloška cesta 7, 1000 Ljubljana, SloveniaDepartment of Molecular and Biomedical Sciences, Jožef Stefan Institute, Jamova 39, 1000 Ljubljana, SloveniaClinical Department of Infectious Diseases, University Hospital of Split, Šoltanska 1, 21000 Split, CroatiaCentre for Research and Knowledge Transfer in Biotechnology, University of Zagreb, Rockefellerova 10, 10000 Zagreb, CroatiaCentre for Clinical Toxicology and Pharmacology, University Medical Centre Ljubljana, Zaloška cesta 7, 1000 Ljubljana, Slovenia<i>Vipera ammodytes</i> (<i>V. ammodytes</i>) is the most venomous European viper. The aim of this study was to compare the clinical efficacy and pharmacokinetic values of intravenous <i>Vipera berus</i> venom-specific (paraspecific) Fab fragments (ViperaTAb) and intramuscular <i>V. ammodytes</i> venom-specific F(ab’)<sub>2</sub> fragments (European viper venom antiserum, also called “Zagreb” antivenom) in <i>V.</i><i>ammodytes</i>-envenomed patients. This was a prospective study of <i>V.</i><i>ammodytes</i>-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’)<sub>2</sub> fragments that were given intramuscularly only on admission. F(ab’)<sub>2</sub> 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 <i>V.</i><i>ammodytes</i>-envenomed patients, the intramuscular use of specific F(ab’)<sub>2</sub> 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.https://www.mdpi.com/2072-6651/13/4/279<i>V. ammodytes</i>nose-horned viperViperaTAbEuropean viper venom antiserum“Zagreb” antivenomFab fragments |
| spellingShingle | Tihana Kurtović Svjetlana Karabuva Damjan Grenc Mojca Dobaja Borak Igor Križaj Boris Lukšić Beata Halassy Miran Brvar Intravenous <i>Vipera berus</i> Venom-Specific Fab Fragments and Intramuscular <i>Vipera ammodytes</i> Venom-Specific F(ab’)<sub>2</sub> Fragments in <i>Vipera ammodytes</i>-Envenomed Patients Toxins <i>V. ammodytes</i> nose-horned viper ViperaTAb European viper venom antiserum “Zagreb” antivenom Fab fragments |
| title | Intravenous <i>Vipera berus</i> Venom-Specific Fab Fragments and Intramuscular <i>Vipera ammodytes</i> Venom-Specific F(ab’)<sub>2</sub> Fragments in <i>Vipera ammodytes</i>-Envenomed Patients |
| title_full | Intravenous <i>Vipera berus</i> Venom-Specific Fab Fragments and Intramuscular <i>Vipera ammodytes</i> Venom-Specific F(ab’)<sub>2</sub> Fragments in <i>Vipera ammodytes</i>-Envenomed Patients |
| title_fullStr | Intravenous <i>Vipera berus</i> Venom-Specific Fab Fragments and Intramuscular <i>Vipera ammodytes</i> Venom-Specific F(ab’)<sub>2</sub> Fragments in <i>Vipera ammodytes</i>-Envenomed Patients |
| title_full_unstemmed | Intravenous <i>Vipera berus</i> Venom-Specific Fab Fragments and Intramuscular <i>Vipera ammodytes</i> Venom-Specific F(ab’)<sub>2</sub> Fragments in <i>Vipera ammodytes</i>-Envenomed Patients |
| title_short | Intravenous <i>Vipera berus</i> Venom-Specific Fab Fragments and Intramuscular <i>Vipera ammodytes</i> Venom-Specific F(ab’)<sub>2</sub> Fragments in <i>Vipera ammodytes</i>-Envenomed Patients |
| title_sort | intravenous i vipera berus i venom specific fab fragments and intramuscular i vipera ammodytes i venom specific f ab sub 2 sub fragments in i vipera ammodytes i envenomed patients |
| topic | <i>V. ammodytes</i> nose-horned viper ViperaTAb European viper venom antiserum “Zagreb” antivenom Fab fragments |
| url | https://www.mdpi.com/2072-6651/13/4/279 |
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