{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T16:14:48Z","timestamp":1790093688453,"version":"4.0.1"},"reference-count":27,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2020,3,16]],"date-time":"2020-03-16T00:00:00Z","timestamp":1584316800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Health and Medical Research Council Centre for Research Excellence","award":["1110343"],"award-info":[{"award-number":["1110343"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>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,\u00a0    C L    , and volume of distribution,\u00a0    V    ) of each toxin were generated based on a log-linear relationship with molecular weight. The concentration\u2013time data of each toxin were simulated for 100 virtual patients using MATLAB and the total concentration\u2013time 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.<\/jats:p>","DOI":"10.3390\/toxins12030188","type":"journal-article","created":{"date-parts":[[2020,3,20]],"date-time":"2020-03-20T07:29:07Z","timestamp":1584689347000},"page":"188","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["The Influence of the Different Disposition Characteristics of Snake Toxins on the Pharmacokinetics of Snake Venom"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7987-6296","authenticated-orcid":false,"given":"Suchaya","family":"Sanhajariya","sequence":"first","affiliation":[{"name":"Clinical Toxicology Research Group, University of Newcastle, Newcastle 2298, Australia"},{"name":"School of Pharmacy, University of Otago, Dunedin 9016, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1519-7419","authenticated-orcid":false,"given":"Geoffrey K.","family":"Isbister","sequence":"additional","affiliation":[{"name":"Clinical Toxicology Research Group, University of Newcastle, Newcastle 2298, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen B.","family":"Duffull","sequence":"additional","affiliation":[{"name":"School of Pharmacy, University of Otago, Dunedin 9016, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,3,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Kasturiratne, A., Wickremasinghe, A.R., de Silva, N., Gunawardena, N.K., Pathmeswaran, A., Premaratna, R., Savioli, L., Lalloo, D.G., and de Silva, H.J. (2008). The global burden of snakebite: A literature analysis and modelling based on regional estimates of envenoming and deaths. PLoS Med., 5.","DOI":"10.1371\/journal.pmed.0050218"},{"key":"ref_2","first-page":"1512","article-title":"Pharmacokinetics of vipera aspis venom after experimental envenomation in rabbits","volume":"268","author":"Audebert","year":"1994","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1016\/0041-0101(93)90151-8","article-title":"Pharmacokinetics of cytotoxin from chinese cobra (naja naja atra) venom","volume":"31","author":"Guo","year":"1993","journal-title":"Toxicon"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"604","DOI":"10.3109\/15563650.2014.914526","article-title":"Pharmacokinetics and pharmacodynamics of the myotoxic venom of pseudechis australis (mulga snake) in the anesthetised rat","volume":"52","author":"Hart","year":"2014","journal-title":"Clin. Toxicol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1016\/j.toxicon.2009.09.018","article-title":"Renal kinetics of bothrops alternatus (urutu) snake venom in rats","volume":"55","author":"Mello","year":"2010","journal-title":"Toxicon"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1201","DOI":"10.1016\/0041-0101(95)00050-V","article-title":"Pharmacokinetics of habutobin in rabbits","volume":"33","author":"Nakamura","year":"1995","journal-title":"Toxicon"},{"key":"ref_7","first-page":"144","article-title":"Lymphatic route of transport and pharmacokinetics of micrurus fulvius (coral snake) venom in sheep","volume":"45","author":"Paniagua","year":"2012","journal-title":"Lymphology"},{"key":"ref_8","first-page":"490","article-title":"Absorption and elimination of viper venom after antivenom administration","volume":"285","author":"Riviere","year":"1998","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"997","DOI":"10.1016\/j.intimp.2013.10.007","article-title":"Pharmacokinetics of cryptelytrops purpureomaculatus (mangrove pit viper) venom following intravenous and intramuscular injections in rabbits","volume":"17","author":"Sim","year":"2013","journal-title":"Int. Immunopharmacol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.toxicon.2013.12.011","article-title":"Pharmacokinetics of the sri lankan hump-nosed pit viper (hypnale hypnale) venom following intravenous and intramuscular injections of the venom into rabbits","volume":"79","author":"Tan","year":"2014","journal-title":"Toxicon"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Yap, M.K., Tan, N.H., Sim, S.M., Fung, S.Y., and Tan, C.H. (2014). Pharmacokinetics of naja sumatrana (equatorial spitting cobra) venom and its major toxins in experimentally envenomed rabbits. [Erratum appears in Plos Negl. Trop. Dis. 2014 sep;8(9):E3277]. PLoS Negl. Trop. Dis., 8.","DOI":"10.1371\/journal.pntd.0002890"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.toxicon.2013.02.017","article-title":"Toxicokinetics of naja sputatrix (javan spitting cobra) venom following intramuscular and intravenous administrations of the venom into rabbits","volume":"68","author":"Yap","year":"2013","journal-title":"Toxicon"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1821","DOI":"10.1016\/S0041-0101(01)00121-0","article-title":"Pharmacokinetics of thrombin-like enzyme from venom of agkistrodon halys ussuriensis emelianov determined by elisa in the rat","volume":"39","author":"Zhao","year":"2001","journal-title":"Toxicon"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Allen, G.E., Brown, S.G.A., Buckley, N.A., O\u2019Leary, M.A., Page, C.B., Currie, B.J., White, J., and Isbister, G.K. (2012). Clinical effects and antivenom dosing in brown snake (pseudonaja spp.) envenoming\u2014australian snakebite project (asp-14). PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0053188"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1093\/jat\/17.4.236","article-title":"Quantitation of venom antigens from european vipers in human serum or urine by elisa","volume":"17","author":"Audebert","year":"1993","journal-title":"J. Anal. Toxicol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1177\/096032719401301006","article-title":"Viper bites in france: Clinical and biological evaluation; kinetics of envenomations","volume":"13","author":"Audebert","year":"1994","journal-title":"Hum. Exp. Toxicol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1016\/j.toxicon.2009.07.034","article-title":"Human anti-snake venom igg antibodies in a previously bitten snake-handler, but no protection against local envenoming","volume":"55","author":"Isbister","year":"2010","journal-title":"Toxicon"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Sanhajariya, S., Duffull, S.B., and Isbister, G.K. (2018). Pharmacokinetics of snake venom. Toxins, 10.","DOI":"10.3390\/toxins10020073"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"605","DOI":"10.4269\/ajtmh.1997.57.605","article-title":"Kinetic study of russell\u2019s viper venom in envenomed patients","volume":"57","author":"Hanvivatvong","year":"1997","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/0035-9203(93)90427-R","article-title":"Accidental envenoming by a gaboon viper (bitis gabonica): The haemostatic disturbances observed and investigation of in vitro haemostatic properties of whole venom","volume":"87","author":"McNally","year":"1993","journal-title":"Trans. R. Soc. Trop. Med. Hyg."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1093\/qjmed\/94.10.551","article-title":"Coagulopathy following lethal and non-lethal envenoming of humans by the south american rattlesnake (crotalus durissus) in brazil","volume":"94","author":"Tomy","year":"2001","journal-title":"QJM"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1016\/j.toxicon.2014.11.231","article-title":"Proteomic investigation of sri lankan hump-nosed pit viper (hypnale hypnale) venom","volume":"93","author":"Tan","year":"2015","journal-title":"Toxicon"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1351","DOI":"10.1023\/A:1015836720294","article-title":"Interspecies scaling of clearance and volume of distribution data for five therapeutic proteins","volume":"8","author":"Mordenti","year":"1991","journal-title":"Pharm. Res."},{"key":"ref_24","unstructured":"Rowland, M., and Tozer, T.N. (2011). Clinical Pharmacokinetics and Pharmacodynamics: Concepts and Applications, Wolters Kluwer Health\/Lippincott William & Wilkins. [4th ed.]."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1211","DOI":"10.1007\/s00228-009-0718-4","article-title":"Population pharmacokinetic analysis of infliximab in patients with ulcerative colitis","volume":"65","author":"Fasanmade","year":"2009","journal-title":"Eur. J. Clin. Pharmacol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"645","DOI":"10.2165\/00003088-200746080-00002","article-title":"Clinical pharmacokinetics and use of infliximab","volume":"46","author":"Klotz","year":"2007","journal-title":"Clin. Pharmacokinet."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1111\/bcp.12313","article-title":"Relationship between inflammation and infliximab pharmacokinetics in rheumatoid arthritis","volume":"78","author":"Ternant","year":"2014","journal-title":"Br. J. Clin. Pharmacol."}],"container-title":["Toxins"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6651\/12\/3\/188\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T09:07:15Z","timestamp":1760173635000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6651\/12\/3\/188"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,3,16]]},"references-count":27,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2020,3]]}},"alternative-id":["toxins12030188"],"URL":"https:\/\/doi.org\/10.3390\/toxins12030188","relation":{},"ISSN":["2072-6651"],"issn-type":[{"value":"2072-6651","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,3,16]]}}}