The Influence of the Different Disposition Characteristics of Snake Toxins on the Pharmacokinetics of Snake Venom.

Suchaya Sanhajariya,Stephen B Duffull,Geoffrey K Isbister

doi:10.3390/toxins12030188

Suchaya Sanhajariya, Stephen B Duffull + Show 1 more

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https://doi.org/10.3390/toxins12030188

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Journal: Toxins	Publication Date: Mar 16, 2020
Citations: 9	License type: CC BY 4.0

Affiliation: University of Newcastle Australia, University of Otago

Abstract

Snake venom is comprised of a combination of different proteins and peptides with a wide range of molecular weights and different disposition processes inherent to each compound. This causes venom to have a complex exposure profile. Our study investigates 1) how each molecular weight fraction (toxin) of venom contributes to the overall time course of the snake venom, and 2) the ability to determine toxin profiles based on the profile of the overall venom only. We undertook an in silico simulation and modelling study. Sixteen variations of venom, comprising of two to nine toxins with different molecular weights were investigated. The pharmacokinetic parameters (i.e., clearance, , and volume of distribution, ) of each toxin were generated based on a log-linear relationship with molecular weight. The concentration–time data of each toxin were simulated for 100 virtual patients using MATLAB and the total concentration–time data of each toxin were modelled using NONMEM. We found that the data of sixteen mixtures were best described by either two- or three-compartment models, despite the venom being made up of more than three different toxins. This suggests that it is generally not possible to determine individual toxin profiles based on measurements of total venom concentrations only.

Highlights

Snake envenomation is defined as the injection of snake venom into human tissue through specialised teeth or “fangs”
An understanding of the time course, denoted pharmacokinetics (PK), of snake venom in humans is crucial for improving snake envenomation management strategies
Each dataset was constructed by summing timed venom concentration data taken from the simulated PK profiles of the individual component toxins

Summary

Introduction

Snake envenomation is defined as the injection of snake venom into human (or animal) tissue through specialised teeth or “fangs”. Snake venom contains a complex mixture of enzymatic and non-enzymatic proteins (toxins), which cause various biological effects. An understanding of the time course, denoted pharmacokinetics (PK), of snake venom in humans is crucial for improving snake envenomation management strategies. In the past three decades, a number of studies had been conducted to investigate the PK of snake venom in animals (e.g., [2,3,4,5,6,7,8,9,10,11,12,13]) and following human envenomation (e.g., [14,15,16,17]). A review of the Toxins 2020, 12, 188; doi:10.3390/toxins12030188 www.mdpi.com/journal/toxins

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