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Pharmacokinetic evaluation of V. ammodytes snakebites treated with currently available antivenoms (CROSBI ID 681227)

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Kurtović, Tihana ; Brvar, Miran ; Karabuva, Svjetlana ; Lang Balija, Maja ; Grenc, Damjan ; Križaj, Igor ; Lukšić, Boris ; Halassy, Beata Pharmacokinetic evaluation of V. ammodytes snakebites treated with currently available antivenoms // 39th Congress of the European Association of Poisons Centres and Clinical Toxicologists (EAPCCT Congress 2019) Napulj, Italija, 22.05.2019-24.05.2019

Podaci o odgovornosti

Kurtović, Tihana ; Brvar, Miran ; Karabuva, Svjetlana ; Lang Balija, Maja ; Grenc, Damjan ; Križaj, Igor ; Lukšić, Boris ; Halassy, Beata

engleski

Pharmacokinetic evaluation of V. ammodytes snakebites treated with currently available antivenoms

Objective: Due to shortage in Zagreb antivenom availability, in Slovenia V. ammodytes bites have been treated with French and UK antivenoms in the recent years. In Croatia, for therapeutic purposes the remaining doses of Zagreb antivenom have still been used. Composition differences between these three antivenoms exist. First, they differ in specificity. Zagreb antivenom (Croatia) is raised against V. ammodytes venom, but is clinically effective and used against all European venomous snakes. Viperfav (France) is raised against the mixture of V. aspis, V. berus and V. ammodytes venoms, but was mostly used against V. aspis and V. berus. ViperaTAb (UK) is raised against V. berus venom solely, and used so far only to treat envenomations caused by V. berus until recently. Second, they differ in type of the active drug component, since Zagreb antivenom and Viperfav are F(ab')2-based, while ViperaTAb is Fab-based preparation. And third, investigated antivenoms have differently prescribed administration routes - intravenous for ViperaTAb and Viperfav or intramuscular for Zagreb antivenom. Aim was to reveal pharmacokinetic profiles of currently available antivenoms in V. ammodytes envenomations and their influence on venom level decrement. Methods: The study represents prospective case series of consecutive patients envenomed by V. ammodytes snakebite and mostly treated with Zagreb antivenom or ViperaTAb in University Hospital of Split or Ljubljana since 2015. In serum samples concentrations of F(ab’)2 or Fab fragments, venom and neurotoxic ammodytoxins were determined. Pharmacokinetic parameters of antivenoms were evaluated whenever possible. Results: Nine patients were treated with Zagreb antivenom and six with ViperaTAb, one of which received Viperfav also. Pharmacokinetic profile differences were revealed. Systemic clearance of ViperaTAb was between 4.3 and 23.2 (mL h-1) / kg. Its distribution and elimination half- lives were in range of 0.4-3.2 h and 12.9-55.9 h, respectively. In the case of Zagreb antivenom, due to prolonged residence time, even the sampling period of 96 h post-treatment was not sufficient for estimation of pharmacokinetic parameters. The exception was 8 days hospitalized patient, revealing systemic clearance of 0.42 (mL h-1) / kg and half-life of 317.2 h. Venom was detected in serum of all patients, in contrary to ammodytoxins. Measured concentrations correlated with the F(ab')2/Fab level, revealing inverse trend in venom- antivenom circulation behavior. Conclusion: Antivenom level was highly dependent on the fabotherapics type and administration route, significantly affecting reappereance and systemic clearance of V. ammodytes venom and its neurotoxic component as well.

Zagreb antivenom ; ViperaTAb ; Viperfav ; immunotherapy ; venom pharmacokinetics ; antivenom pharmacokinetics

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Podaci o prilogu

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Podaci o skupu

39th Congress of the European Association of Poisons Centres and Clinical Toxicologists (EAPCCT Congress 2019)

poster

22.05.2019-24.05.2019

Napulj, Italija

Povezanost rada

Biotehnologija u biomedicini (prirodno područje, biomedicina i zdravstvo, biotehničko područje)