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Pharmaceutics
Volume 17
Issue 2
10.3390/pharmaceutics17020212
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Article

Pharmacokinetics of Snake Antivenom Following Intravenous and Intramuscular Administration in Envenomed Large Animal Model

by
Erika Gamulin
1,
Sanja Mateljak Lukačević
1,
Maja Lang Balija
1,
Ana Smajlović
2,
Dražen Vnuk
2,
Jadranka Gulan Harcet
3,
Maja Tomičić
3,
Ana Hećimović
3,
Beata Halassy
1 and
Tihana Kurtović
1,*
1
Centre for Research and Knowledge Transfer in Biotechnology, University of Zagreb, Rockefellerova 10, HR-10000 Zagreb, Croatia
2
Clinic for Surgery, Orthopaedics and Ophthalmology, Faculty of Veterinary Medicine, University of Zagreb, Heinzelova 55, HR-10000 Zagreb, Croatia
3
Croatian Institute of Transfusion Medicine, Petrova 3, HR-10000 Zagreb, Croatia
*
Author to whom correspondence should be addressed.
Pharmaceutics 2025, 17(2), 212; https://doi.org/10.3390/pharmaceutics17020212
Submission received: 8 January 2025 / Revised: 27 January 2025 / Accepted: 4 February 2025 / Published: 7 February 2025
(This article belongs to the Special Issue Mechanisms of Drug Interactions: Pharmacodynamics and Pharmacokinetics)
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Abstract

Background: The parenteral administration of antivenoms is the mainstay in snakebite envenoming therapy. The standardized protocol does not exist, but it is agreed that the intravenous (i.v.) route is more effective than the others, especially the intramuscular (i.m.) route, based on the monitoring of venom/antivenom pharmacokinetics in the systemic circulation. Recent evidence suggests that the lymphatic system may be crucial in abolishing venom action. Methods: A preclinical study was performed to determine the optimal administration route with emphasis on venom/antivenom interplay in both the blood and lymph of experimentally envenomed sheep. Timed level measurements were used to compare the antivenom effect on the decrement of venom quantities in both relevant body compartments. Hematological and coagulation parameters, as well as proportions of developed anti-antivenom IgGs, were evaluated. Results: The i.m. antivenom resulted in faster and greater lymphatic absorption and complete neutralization of the venom, whereas the i.v. antivenom only slowed its absorption. The total amount of venom reaching the lymph (AUC0-t) was two times lower after i.m. administration. In the systemic circulation, i.m. antivenom had a lower peak concentration (cmax) and a longer time to reach it (tmax). However, the total venom exposure was three times lower than with i.v. antivenom. Irrespective of the treatment approach, both groups showed improvement in blood disorders with no significant difference in humoral response against equine F(ab’)2 fragments. Conclusions: I.m. administration proved to be a viable option for the snakebite management.
Keywords: Zagreb antivenom; Vipera ammodytes venom; administration route; pharmacokinetics; lymphatic system; systemic circulation; immunotherapy; drug efficacy Zagreb antivenom; Vipera ammodytes venom; administration route; pharmacokinetics; lymphatic system; systemic circulation; immunotherapy; drug efficacy

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MDPI and ACS Style

Gamulin, E.; Mateljak Lukačević, S.; Lang Balija, M.; Smajlović, A.; Vnuk, D.; Gulan Harcet, J.; Tomičić, M.; Hećimović, A.; Halassy, B.; Kurtović, T. Pharmacokinetics of Snake Antivenom Following Intravenous and Intramuscular Administration in Envenomed Large Animal Model. Pharmaceutics 2025, 17, 212. https://doi.org/10.3390/pharmaceutics17020212

AMA Style

Gamulin E, Mateljak Lukačević S, Lang Balija M, Smajlović A, Vnuk D, Gulan Harcet J, Tomičić M, Hećimović A, Halassy B, Kurtović T. Pharmacokinetics of Snake Antivenom Following Intravenous and Intramuscular Administration in Envenomed Large Animal Model. Pharmaceutics. 2025; 17(2):212. https://doi.org/10.3390/pharmaceutics17020212

Chicago/Turabian Style

Gamulin, Erika, Sanja Mateljak Lukačević, Maja Lang Balija, Ana Smajlović, Dražen Vnuk, Jadranka Gulan Harcet, Maja Tomičić, Ana Hećimović, Beata Halassy, and Tihana Kurtović. 2025. "Pharmacokinetics of Snake Antivenom Following Intravenous and Intramuscular Administration in Envenomed Large Animal Model" Pharmaceutics 17, no. 2: 212. https://doi.org/10.3390/pharmaceutics17020212

APA Style

Gamulin, E., Mateljak Lukačević, S., Lang Balija, M., Smajlović, A., Vnuk, D., Gulan Harcet, J., Tomičić, M., Hećimović, A., Halassy, B., & Kurtović, T. (2025). Pharmacokinetics of Snake Antivenom Following Intravenous and Intramuscular Administration in Envenomed Large Animal Model. Pharmaceutics, 17(2), 212. https://doi.org/10.3390/pharmaceutics17020212

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