Background: Snake envenomation can result in devastating local and systemic effects, which requires hospitalisation, and on occasion permanent disabilities and fatality in severe cases . The management of snake envenomation involves supportive treatment and administration of snake specific antivenoms to neutralise free venom and prevent further envenomation. The knowledge of snake venom pharmacokinetics in humans is important for optimisation of antivenom therapy, by establishing an optimal dose to bind all free venom, and determine the time post-bite in which antivenom remains effective.
Aim: To explore the pharmacokinetics of snake venom in humans by performing a meta-analysis of the reported time course of snake venom concentration in people with snakebites. It is intended that the quantitative information obtained from this study will provide a useful basis for the design and analysis of future clinical studies that will address the pharmacokinetics of snake venom in humans.
Materials and Methods: Literature searches were conducted using EMBASE (1974-present) and Medline (1946-present). Snake venom concentration data post-bite in the absence of antivenom administration were extracted 1) from values reported in the text of the study report, or 2) by digitising data from graphs published in the study report using WebPlotDigitizer v3.12 software (available at: http://arohatgi.info/WebPlotDigitizer/). Extracted data were then visualised using Microsoft Excel, and NONMEM was used to develop population pharmacokinetic model and estimate parameter values.
Results: The meta-analysis included 24 out of 666 initially identified studies, which contained sufficient information and timed venom concentrations in the absence of antivenom therapy for data extraction. The extracted dataset consisted of 145 patients who were bitten by snakes from either the Elapidae or Viperidae family who provided 218 plasma snake venom concentrations. The dataset was sparse, in terms of numbers of samples per patient, with a large magnitude of difference between snake concentration data. A one-compartment model with zero-order input and first-order elimination best described the literature-derived data. The elimination half-life was 9.71 ± 1.29 hours which is not inconsistent with allometrically scaled values from animal data. Snake family was found to be a significant covariate on the relative dose of venom received by the patient with snakes from the Vierpidae family delivering approximately 75% more dose per bite.
Conclusion: From this meta-analysis we were able to develop a preliminary pharmacokinetic model of snake venom. Future exploration of the relationship between pharmacokinetic parameters and covariates is required to identifying other important factors that may influence the pharmacokinetic profile of snake venom and to determine the dose and time window for antivenom administration.
1. Warrell, D.A.; Gutiérrez, J.M.; Organization, W.H. Rabies and envenomings: A neglected public health issue : Report of a consultative meeting. World Health Organization: Geneva, 2007.